Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Dynamin, a membrane-remodelling GTPase

Key Points

  • Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts.

  • The mechanisms by which dynamin drives membrane fission have been the subject of intense debate. Recent crystallographic and cryo-electron microscopy studies of dynamin and DLPs support a model in which dynamin polymerization serves to bring two GTPase domains together, which allows GTP hydrolysis and the conformational changes in dynamin that are necessary for helix constriction and membrane fission.

  • The role of dynamin is best defined during clathrin-dependent endocytosis and is essential only for a late step when membrane fission occurs.

  • Gene-knockout studies in mice and the cells derived from them have provided numerous insights into dynamin function and the specific roles of the three dynamin isoforms. Dynamin 2 is ubiquitously expressed and has a housekeeping role in membrane dynamics. By contrast, dynamin 1 and dynamin 3 are specific to the nervous system and, although neither is essential for supporting a specific form of endocytosis at synapses, they may be important for allowing clathrin-mediated endocytosis to function over a very broad range of neuronal activities.

  • Roles of abnormal dynamin function in genetic disease have begun to emerge. Whereas mutations in dynamin 2 show links to tissue-specific diseases, mutations in dynamin 1 specifically affect the nervous system.

Abstract

Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sites of action of dynamin and DLPs in a mammalian cell.
Figure 2: Structure of dynamin and putative mechanism of dynamin-mediated membrane fission.
Figure 3: Dynamin and clathrin-mediated endocytosis.
Figure 4: Dynamin participates in synaptic vesicle recycling at neuronal synapses.

References

  1. McMahon, H. T. & Boucrot, E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nature Rev. Mol. Cell Biol. 12, 517–533 (2011).

    Article  CAS  Google Scholar 

  2. Mercer, J., Schelhaas, M. & Helenius, A. Virus entry by endocytosis. Ann. Rev. Biochem. 79, 803–833 (2010).

    Article  CAS  PubMed  Google Scholar 

  3. Scita, G. & Di Fiore, P. P. The endocytic matrix. Nature 463, 464–473 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Howes, M. T., Mayor, S. & Parton, R. G. Molecules, mechanisms, and cellular roles of clathrin-independent endocytosis. Curr. Opin. Cell Biol. 22, 519–527 (2010).

    Article  CAS  PubMed  Google Scholar 

  5. Koenig, J. H. & Ikeda, K. Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval. J. Neurosci. 9, 3844–3860 (1989). Shows the depletion of synaptic vesicles and accumulation of collared pits in the plasma membrane of shibire mutant synapses upon acute stimulation at the non-permissive temperature, and thus nicely demonstrates the critical role played by dynamin in synaptic vesicle recycling.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shpetner, H. S. & Vallee, R. B. Identification of dynamin, a novel mechanochemical enzyme that mediates interactions between microtubules. Cell 59, 421–432 (1989).

    Article  CAS  PubMed  Google Scholar 

  7. van der Bliek, A. M. & Meyerowitz, E. M. Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 351, 411–414 (1991).

    Article  CAS  PubMed  Google Scholar 

  8. Chen, M. S. et al. Multiple forms of dynamin are encoded by shibire, a Drosophila gene involved in endocytosis. Nature 351, 583–586 (1991). References 7 and 8 identify dynamin as the product of the shibire gene and set the stage for studies of dynamin as a critical endocytic protein.

    Article  CAS  PubMed  Google Scholar 

  9. Obar, R. A., Collins, C. A., Hammarback, J. A., Shpetner, H. S. & Vallee, R. B. Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins. Nature 347, 256–261 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Takei, K., McPherson, P. S., Schmid, S. L. & De Camilli, P. Tubular membrane invaginations coated by dynamin rings are induced by GTP-γS in nerve terminals. Nature 374, 186–190 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Hinshaw, J. E. & Schmid, S. L. Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. Nature 374, 190–192 (1995). References 10 and 11 show the ability of dynamin to polymerize into helices around membrane templates and at the base of clathrin-coated pits, leading to a model wherein the assembly of dynamin into helical polymers followed by conformational changes triggered by GTP hydrolysis could lead to membrane fission.

    Article  CAS  PubMed  Google Scholar 

  12. Damke, H., Baba, T., Warnock, D. E. & Schmid, S. L. Induction of mutant dynamin specifically blocks endocytic coated vesicle formation. J. Cell Biol. 127, 915–934 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Herskovits, J. S., Burgess, C. C., Obar, R. A. & Vallee, R. B. Effects of mutant rat dynamin on endocytosis. J. Cell Biol. 122, 565–578 (1993).

    Article  CAS  PubMed  Google Scholar 

  14. van der Bliek, A. M. et al. Mutations in human dynamin block an intermediate stage in coated vesicle formation. J. Cell Biol. 122, 553–563 (1993). Demonstrates that dynamin mutants with impaired GTP binding and hydrolysis exert dominant-negative effects on clathrin-mediated endocytosis.

    Article  CAS  PubMed  Google Scholar 

  15. Marks, B. et al. GTPase activity of dynamin and resulting conformation change are essential for endocytosis. Nature 410, 231–235 (2001). Shows the importance of GTP hydrolysis by dynamin in the endocytic actions of dynamin, arguing against a regulatory GTPase-like function for dynamin.

    Article  CAS  PubMed  Google Scholar 

  16. Cao, H., Garcia, F. & McNiven, M. A. Differential distribution of dynamin isoforms in mammalian cells. Mol. Biol. Cell 9, 2595–2609 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ferguson, S. M. et al. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis. Science 316, 570–574 (2007). Reveals using dynamin 1-knockout mice that, contrary to expectations, dynamin 1 is not required for the making of synaptic vesicles but rather serves to enhance the efficiency of this clathrin-mediated process at synapses.

    Article  CAS  PubMed  Google Scholar 

  18. Nakata, T. et al. Predominant and developmentally regulated expression of dynamin in neurons. Neuron 7, 461–469 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. Ferguson, S. M. et al. Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev. Cell 17, 811–822 (2009). Analyses the endocytic intermediates that accumulate in cells lacking dynamin and indicates a role for F-actin in the recruitment of BAR domain-containing proteins to the tubular neck of clathrin-coated pits.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liu, Y. W., Surka, M. C., Schroeter, T., Lukiyanchuk, V. & Schmid, S. L. Isoform and splice-variant specific functions of dynamin-2 revealed by analysis of conditional knock-out cells. Mol. Biol. Cell 19, 5347–5359 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cook, T. A., Urrutia, R. & McNiven, M. A. Identification of dynamin 2, an isoform ubiquitously expressed in rat tissues. Proc. Natl Acad. Sci. USA 91, 644–648 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Raimondi, A. et al. Overlapping role of dynamin isoforms in synaptic vesicle endocytosis. Neuron 70, 1100–1114 (2011). Reports that, although dynamin 3-knockout mice lack a discernible phenotype, analysis of dynamin 1 and dynamin 3 double-knockout mice reveals a role for both dynamins in the recycling of synaptic vesicles.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Clark, S. G., Shurland, D. L., Meyerowitz, E. M., Bargmann, C. I. & van der Bliek, A. M. A dynamin GTPase mutation causes a rapid and reversible temperature-inducible locomotion defect in C. elegans. Proc. Natl Acad. Sci. USA 94, 10438–10443 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xue, J. et al. Calcineurin selectively docks with the dynamin Ixb splice variant to regulate activity-dependent bulk endocytosis. J. Biol. Chem. 286, 30295–30303 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bodmer, D., Ascano, M. & Kuruvilla, R. Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth. Neuron 70, 1085–1099 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pizzato, M. et al. Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef. Proc. Natl Acad. Sci. USA 104, 6812–6817 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gray, N. W. et al. Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer. Curr. Biol. 13, 510–515 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. Liu, Y. W. et al. Differential curvature sensing and generating activities of dynamin isoforms provide opportunities for tissue-specific regulation. Proc. Natl Acad. Sci. USA 108, E234–E242 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Gasper, R., Meyer, S., Gotthardt, K., Sirajuddin, M. & Wittinghofer, A. It takes two to tango: regulation of G proteins by dimerization. Nature Rev. Mol. Cell Biol. 10, 423–429 (2009).

    Article  CAS  Google Scholar 

  30. Chappie, J. S., Acharya, S., Leonard, M., Schmid, S. L. & Dyda, F. G. domain dimerization controls dynamin's assembly-stimulated GTPase activity. Nature 465, 435–440 (2010). Reveals, through an analysis of the structure of a dynamin G domain–GED fusion protein, a need for dynamin G domain dimerization in mediating GTP hydrolysis and proposes that such dimerization occurs between rungs of the dynamin helix.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Faelber, K. et al. Crystal structure of nucleotide-free dynamin. Nature 477, 561–566 (2011).

    Article  CAS  Google Scholar 

  32. Ford, M. G. J., Jenni, S. & Nunnari, J. The crystal structure of dynamin. Nature 477, 556–560 (2011). Describes the first crystal structures of nearly full-length dynamin and reveals extensive interactions that support dynamin assembly into polymeric helices.

    Article  CAS  Google Scholar 

  33. Chappie, J. S. et al. A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke. Cell 147, 209–222 (2011). Comparisons between dynamin G domain–GED fusion protein structures that mimic the GTP-bound state and ones that mimic a transition state suggest that large conformational changes accompany GTP hydrolysis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gao, S. et al. Structural basis of oligomerization in the stalk region of dynamin-like MxA. Nature 465, 502–506 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Ingerman, E. et al. Dnm1 forms spirals that are structurally tailored to fit mitochondria. J. Cell Biol. 170, 1021–1027 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bian, X. et al. Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes. Proc. Natl Acad. Sci. USA 108, 3976–3981 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Byrnes, L. J. & Sondermann, H. Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A. Proc. Natl Acad. Sci. USA 108, 2216–2221 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chappie, J. S. et al. A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke. Cell 147, 209–222 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sever, S., Muhlberg, A. B. & Schmid, S. L. Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis. Nature 398, 481–486 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Low, H. H. & Lowe, J. A bacterial dynamin-like protein. Nature 444, 766–769 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Narayanan, R., Leonard, M., Song, B. D., Schmid, S. L. & Ramaswami, M. An internal GAP domain negatively regulates presynaptic dynamin in vivo: a two-step model for dynamin function. J. Cell Biol. 169, 117–126 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ferguson, K. M., Lemmon, M. A., Schlessinger, J. & Sigler, P. B. Crystal structure at 2.2 Å resolution of the pleckstrin homology domain from human dynamin. Cell 79, 199–209 (1994).

    Article  CAS  PubMed  Google Scholar 

  43. Zheng, J. et al. Identification of the binding site for acidic phospholipids on the PH domain of dynamin: implications for stimulation of GTPase activity. J. Mol. Biol. 255, 14–21 (1996).

    Article  CAS  PubMed  Google Scholar 

  44. Lee, A., Frank, D. W., Marks, M. S. & Lemmon, M. A. Dominant-negative inhibition of receptor-mediated endocytosis by a dynamin-1 mutant with a defective pleckstrin homology domain. Curr. Biol. 9, 261–264 (1999).

    Article  PubMed  Google Scholar 

  45. Vallis, Y., Wigge, P., Marks, B., Evans, P. R. & McMahon, H. T. Importance of the pleckstrin homology domain of dynamin in clathrin-mediated endocytosis. Curr. Biol. 9, 257–260 (1999).

    Article  CAS  PubMed  Google Scholar 

  46. Bethoney, K. A., King, M. C., Hinshaw, J. E., Ostap, E. M. & Lemmon, M. A. A possible effector role for the pleckstrin homology (PH) domain of dynamin. Proc. Natl Acad. Sci. USA 106, 13359–13364 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ramachandran, R. et al. Membrane insertion of the pleckstrin homology domain variable loop 1 is critical for dynamin-catalyzed vesicle scission. Mol. Biol. Cell 20, 4630–4639 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Anggono, V. et al. Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nature Neurosci. 9, 752–760 (2006). Finds that syndapin is the major dynamin-interacting protein in the brain and that this interaction is regulated by dynamin phosphorylation, potentially coupling this interaction to the activity status of neurons.

    Article  CAS  PubMed  Google Scholar 

  49. Grabs, D. et al. The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. J. Biol. Chem. 272, 13419–13425 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Lundmark, R. & Carlsson, S. R. Regulated membrane recruitment of dynamin-2 mediated by sorting nexin 9. J. Biol. Chem. 279, 42694–42702 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Shpetner, H. S., Herskovits, J. S. & Vallee, R. B. A binding site for SH3 domains targets dynamin to coated pits. J. Biol. Chem. 271, 13–16 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Mooren, O. L., Kotova, T. I., Moore, A. J. & Schafer, D. A. Dynamin2 GTPase and cortactin remodel actin filaments. J. Biol. Chem. 284, 23995–24005 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Roux, A. et al. Membrane curvature controls dynamin polymerization. Proc. Natl Acad. Sci. USA 107, 4141–4146 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Stowell, M. H., Marks, B., Wigge, P. & McMahon, H. T. Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring. Nature Cell Biol. 1, 27–32 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Roux, A., Uyhazi, K., Frost, A. & De Camilli, P. GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission. Nature 441, 528–531 (2006). Visualizes dynamin-mediated membrane fission in an in vitro assay and reveals contributions by dynamin-mediated membrane constriction and membrane tension to membrane fission.

    Article  CAS  PubMed  Google Scholar 

  56. Sweitzer, S. M. & Hinshaw, J. E. Dynamin undergoes a GTP-dependent conformational change causing vesiculation. Cell 93, 1021–1029 (1998).

    Article  CAS  PubMed  Google Scholar 

  57. Takei, K. et al. Generation of coated intermediates of clathrin-mediated endocytosis on protein-free liposomes. Cell 94, 131–141 (1998).

    Article  CAS  PubMed  Google Scholar 

  58. Ramachandran, R. et al. The dynamin middle domain is critical for tetramerization and higher-order self-assembly. EMBO J. 26, 559–566 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Low, H. H. & Lowe, J. Dynamin architecture — from monomer to polymer. Curr. Opin. Struct. Biol. 20, 791–798 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Wu, M. et al. Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system. Nature Cell Biol. 12, 902–908 (2010).

    Article  CAS  PubMed  Google Scholar 

  61. Bashkirov, P. V. et al. GTPase cycle of dynamin is coupled to membrane squeeze and release, leading to spontaneous fission. Cell 135, 1276–1286 (2008). Describes an in vitro membrane fission assay that suggests a role for repeated assembly and disassembly of short dynamin scaffolds in the triggering of membrane fission.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Danino, D., Moon, K. H. & Hinshaw, J. E. Rapid constriction of lipid bilayers by the mechanochemical enzyme dynamin. J. Struct. Biol. 147, 259–267 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Pucadyil, T. J. & Schmid, S. L. Real-time visualization of dynamin-catalyzed membrane fission and vesicle release. Cell 135, 1263–1275 (2008). Reports an in vitro assay that closely mimics the in vivo situation by allowing observation of dynamin-mediated membrane fission in the continuous presence of GTP, and reveals the fluctuating assembly and disassembly of dynamin leading up to membrane fission.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ghosh, A., Praefcke, G. J., Renault, L., Wittinghofer, A. & Herrmann, C. How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP. Nature 440, 101–104 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Binns, D. D. et al. The mechanism of GTP hydrolysis by dynamin II: a transient kinetic study. Biochemistry 39, 7188–7196 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Krishnan, K. S. et al. Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Neuron 30, 197–210 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. Taylor, M. J., Perrais, D. & Merrifield, C. J. A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. PLoS Biol. 9, e1000604 (2011). Details a systematic analysis of the recruitment of a large collection of proteins to clathrin and their relationship to the membrane fission event.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Collins, A., Warrington, A., Taylor, K. A. & Svitkina, T. Structural organization of the actin cytoskeleton at sites of clathrin-mediated endocytosis. Curr. Biol. 21, 1167–1175 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Liu, J., Sun, Y., Drubin, D. G. & Oster, G. F. The mechanochemistry of endocytosis. PLoS Biol. 7, e1000204 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Chang-Ileto, B. et al. Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission. Dev. Cell 20, 206–218 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Frost, A., Unger, V. M. & De Camilli, P. The BAR domain superfamily: membrane-molding macromolecules. Cell 137, 191–196 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Farsad, K. et al. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J. Cell Biol. 155, 193–200 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Takei, K., Slepnev, V. I., Haucke, V. & De Camilli, P. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nature Cell Biol. 1, 33–39 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Huang, F., Khvorova, A., Marshall, W. & Sorkin, A. Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. J. Biol. Chem. 279, 16657–16661 (2004).

    Article  CAS  PubMed  Google Scholar 

  75. Henne, W. M. et al. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science 328, 1281–1284 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Traub, L. M. Tickets to ride: selecting cargo for clathrin-regulated internalization. Nature Rev. Mol. Cell Biol. 10, 583–596 (2009).

    Article  CAS  Google Scholar 

  77. Kirchhausen, T. Adaptors for clathrin-mediated traffic. Annu. Rev. Cell Dev. Biol. 15, 705–732 (1999).

    Article  CAS  PubMed  Google Scholar 

  78. Saffarian, S., Cocucci, E. & Kirchhausen, T. Distinct dynamics of endocytic clathrin-coated pits and coated plaques. PLoS Biol. 7, e1000191 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Itoh, T. et al. Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins. Dev. Cell 9, 791–804 (2005).

    Article  CAS  PubMed  Google Scholar 

  80. Perera, R. M., Zoncu, R., Lucast, L., De Camilli, P. & Toomre, D. Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages. Proc. Natl Acad. Sci. USA 103, 19332–19337 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Damke, H., Binns, D. D., Ueda, H., Schmid, S. L. & Baba, T. Dynamin GTPase domain mutants block endocytic vesicle formation at morphologically distinct stages. Mol. Biol. Cell 12, 2578–2589 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Massol, R., Boll, W., Griffin, A. M. & Kirchhausen, T. burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating. Proc. Natl Acad. Sci. USA 103, 10265–10270 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Barylko, B. et al. Synergistic activation of dynamin GTPase by Grb2 and phosphoinositides. J. Biol. Chem 273, 3791–3797 (1998).

    Article  CAS  PubMed  Google Scholar 

  84. Zoncu, R. et al. Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proc. Natl Acad. Sci. USA 104, 3793–3798 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Gu, C. et al. Direct dynamin-actin interactions regulate the actin cytoskeleton. EMBO J. 29, 3593–3606 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Conibear, E. Converging views of endocytosis in yeast and mammals. Curr. Opin. Cell Biol. 22, 513–518 (2010).

    Article  CAS  PubMed  Google Scholar 

  87. Kaksonen, M., Toret, C. P. & Drubin, D. G. A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell 123, 305–320 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Nannapaneni, S. et al. The yeast dynamin-like protein Vps1:vps1 mutations perturb the internalization and the motility of endocytic vesicles and endosomes via disorganization of the actin cytoskeleton. Eur. J. Cell Biol. 89, 499–508 (2010).

    Article  CAS  PubMed  Google Scholar 

  89. Smaczynska-de, R. II. et al. Yeast dynamin Vps1 and amphiphysin Rvs167 function together during endocytosis. Traffic 14 Nov 2011 (doi:10.1111/j.1600-0854.2011.01311.x).

    Article  PubMed  CAS  Google Scholar 

  90. Kaksonen, M., Toret, C. P. & Drubin, D. G. Harnessing actin dynamics for clathrin-mediated endocytosis. Nature Rev. Mol. Cell Biol. 7, 404–414 (2006).

    Article  CAS  Google Scholar 

  91. Aghamohammadzadeh, S. & Ayscough, K. R. Differential requirements for actin during yeast and mammalian endocytosis. Nature Cell Biol. 11, 1039–1042 (2009).

    Article  CAS  PubMed  Google Scholar 

  92. Pelkmans, L., Puntener, D. & Helenius, A. Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science 296, 535–539 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Henley, J. R., Krueger, E. W., Oswald, B. J. & McNiven, M. A. Dynamin-mediated internalization of caveolae. J. Cell Biol. 141, 85–99 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Jones, S. M., Howell, K. E., Henley, J. R., Cao, H. & McNiven, M. A. Role of dynamin in the formation of transport vesicles from the trans-Golgi network. Science 279, 573–577 (1998).

    Article  CAS  PubMed  Google Scholar 

  95. Derivery, E. et al. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Dev. Cell 17, 712–723 (2009).

    Article  CAS  PubMed  Google Scholar 

  96. Kreitzer, G., Marmorstein, A., Okamoto, P., Vallee, R. & Rodriguez-Boulan, E. Kinesin and dynamin are required for post-Golgi transport of a plasma-membrane protein. Nature Cell Biol. 2, 125–127 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Mesaki, K., Tanabe, K., Obayashi, M., Oe, N. & Takei, K. Fission of tubular endosomes triggers endosomal acidification and movement. PloS ONE 6, e19764 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Rothman, J. H., Raymond, C. K., Gilbert, T., O'Hara, P. J. & Stevens, T. H. A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting. Cell 61, 1063–1074 (1990).

    Article  CAS  PubMed  Google Scholar 

  99. Yarar, D., Waterman-Storer, C. M. & Schmid, S. L. A dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis. Mol. Biol. Cell 16, 964–975 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Boulant, S., Kural, C., Zeeh, J. C., Ubelmann, F. & Kirchhausen, T. Actin dynamics counteract membrane tension during clathrin-mediated endocytosis. Nature Cell Biol. 13, 1124–1131 (2011).

    Article  CAS  PubMed  Google Scholar 

  101. Schlunck, G. et al. Modulation of Rac localization and function by dynamin. Mol. Biol. Cell 15, 256–267 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Krueger, E. W., Orth, J. D., Cao, H. & McNiven, M. A. A dynamin-cortactin-Arp2/3 complex mediates actin reorganization in growth factor-stimulated cells. Mol. Biol. Cell 14, 1085–1096 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gold, E. S. et al. Dynamin 2 is required for phagocytosis in macrophages. J. Exp. Med. 190, 1849–1856 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Baldassarre, M. et al. Dynamin participates in focal extracellular matrix degradation by invasive cells. Mol. Biol. Cell 14, 1074–1084 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ochoa, G. C. et al. A functional link between dynamin and the actin cytoskeleton at podosomes. J. Cell Biol. 150, 377–389 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Lee, E. & De Camilli, P. Dynamin at actin tails. Proc. Natl Acad. Sci. USA 99, 161–166 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Orth, J. D., Krueger, E. W., Cao, H. & McNiven, M. A. The large GTPase dynamin regulates actin comet formation and movement in living cells. Proc. Natl Acad. Sci. USA 99, 167–172 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Unsworth, K. E. et al. Dynamin is required for F-actin assembly and pedestal formation by enteropathogenic Escherichia coli (EPEC). Cell. Microbiol. 9, 438–449 (2007).

    Article  CAS  PubMed  Google Scholar 

  109. Kubler, E. & Riezman, H. Actin and fimbrin are required for the internalization step of endocytosis in yeast. EMBO J. 12, 2855–2862 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Gomez, T. S. et al. Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Nature Immunol. 6, 261–270 (2005).

    Article  CAS  Google Scholar 

  111. Yamada, H. et al. Dynasore, a dynamin inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments. Biochem. Biophys. Res. Commun. 390, 1142–1148 (2009).

    Article  CAS  PubMed  Google Scholar 

  112. Tanabe, K. & Takei, K. Dynamic instability of microtubules requires dynamin 2 and is impaired in a Charcot–Marie–Tooth mutant. J. Cell Biol. 185, 939–948 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Skop, A. R., Liu, H., Yates, J. 3rd, Meyer, B. J. & Heald, R. Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. Science 305, 61–66 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Chircop, M. et al. Phosphorylation of dynamin II at serine-764 is associated with cytokinesis. Biochim. Biophys. Acta 1813, 1689–1699 (2011).

    Article  CAS  PubMed  Google Scholar 

  115. Thompson, H. M., Skop, A. R., Euteneuer, U., Meyer, B. J. & McNiven, M. A. The large GTPase dynamin associates with the spindle midzone and is required for cytokinesis. Curr. Biol. 12, 2111–2117 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Goss, J. W. & Toomre, D. K. Both daughter cells traffic and exocytose membrane at the cleavage furrow during mammalian cytokinesis. J. Cell Biol. 181, 1047–1054 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Gromley, A. et al. Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell 123, 75–87 (2005).

    Article  CAS  PubMed  Google Scholar 

  118. Morita, E. et al. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 26, 4215–4227 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Tan, T. C. et al. Cdk5 is essential for synaptic vesicle endocytosis. Nature Cell Biol. 5, 701–710 (2003).

    Article  CAS  PubMed  Google Scholar 

  120. Kashatus, D. F. et al. RALA and RALBP1 regulate mitochondrial fission at mitosis. Nature Cell Biol. 13, 1108–1115 (2011).

    Article  CAS  PubMed  Google Scholar 

  121. Sorkin, A. & von Zastrow, M. Endocytosis and signalling: intertwining molecular networks. Nature Rev. Mol. Cell Biol. 10, 609–622 (2009).

    Article  CAS  Google Scholar 

  122. Sigismund, S. et al. Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev. Cell 15, 209–219 (2008).

    Article  CAS  PubMed  Google Scholar 

  123. Vieira, A. V., Lamaze, C. & Schmid, S. L. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274, 2086–2089 (1996).

    Article  CAS  PubMed  Google Scholar 

  124. Windler, S. L. & Bilder, D. Endocytic internalization routes required for Delta/Notch signaling. Curr. Biol. 20, 538–543 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Poodry, C. A. shibire, a neurogenic mutant of Drosophila. Dev. Biol. 138, 464–472 (1990).

    Article  CAS  PubMed  Google Scholar 

  126. Polo, S. & Di Fiore, P. P. Endocytosis conducts the cell signaling orchestra. Cell 124, 897–900 (2006).

    Article  CAS  PubMed  Google Scholar 

  127. Shen, H. et al. Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin. Mol. Biol. Cell 22, 493–502 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Chircop, M. et al. Inhibition of dynamin by dynole 34–2 induces cell death following cytokinesis failure in cancer cells. Mol. Cancer Ther. 10, 1553–1562 (2011).

    Article  CAS  PubMed  Google Scholar 

  129. Goldenthal, K. L., Pastan, I. & Willingham, M. C. Initial steps in receptor-mediated endocytosis. The influence of temperature on the shape and distribution of plasma membrane clathrin-coated pits in cultured mammalian cells. Exp. Cell Res. 152, 558–564 (1984).

    Article  CAS  PubMed  Google Scholar 

  130. Dittman, J. & Ryan, T. A. Molecular circuitry of endocytosis at nerve terminals. Annu. Rev. Cell Dev. Biol. 25, 133–160 (2009).

    Article  CAS  PubMed  Google Scholar 

  131. Newton, A. J., Kirchhausen, T. & Murthy, V. N. Inhibition of dynamin completely blocks compensatory synaptic vesicle endocytosis. Proc. Natl Acad. Sci. USA 103, 17955–17960 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Shupliakov, O. et al. Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions. Science 276, 259–263 (1997).

    Article  CAS  PubMed  Google Scholar 

  133. Sundborger, A. et al. An endophilin–dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling. J. Cell Sci. 124, 133–143 (2011).

    Article  CAS  PubMed  Google Scholar 

  134. Xu, J. et al. GTP-independent rapid and slow endocytosis at a central synapse. Nature Neurosci. 11, 45–53 (2008).

    Article  CAS  PubMed  Google Scholar 

  135. Yamashita, T., Hige, T. & Takahashi, T. Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse. Science 307, 124–127 (2005).

    Article  CAS  PubMed  Google Scholar 

  136. Lou, X., Paradise, S., Ferguson, S. M. & De Camilli, P. Selective saturation of slow endocytosis at a giant glutamatergic central synapse lacking dynamin 1. Proc. Natl Acad. Sci. USA 105, 17555–17560 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Isaka, F. et al. Ectopic expression of the bHLH gene Math1 disturbs neural development. Eur. J. Neurosci. 11, 2582–2588 (1999).

    Article  CAS  PubMed  Google Scholar 

  138. Dewachter, I. et al. Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J. Neurosci. 22, 3445–3453 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Cousin, M. A. & Robinson, P. J. The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis. Trends Neurosci. 24, 659–665 (2001).

    Article  CAS  PubMed  Google Scholar 

  140. Lee, S. Y., Wenk, M. R., Kim, Y., Nairn, A. C. & De Camilli, P. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses. Proc. Natl Acad. Sci. USA 101, 546–551 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. McPherson, P. S., Takei, K., Schmid, S. L. & De Camilli, P. p145, a major Grb2-binding protein in brain, is co-localized with dynamin in nerve terminals where it undergoes activity-dependent dephosphorylation. J. Biol. Chem. 269, 30132–30139 (1994).

    Article  CAS  PubMed  Google Scholar 

  142. Lu, J. et al. Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer. Neuron 55, 874–889 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Carroll, R. C. et al. Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc. Natl Acad. Sci. USA 96, 14112–14117 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Perez-Otano, I. et al. Endocytosis and synaptic removal of NR3A-containing NMDA receptors by PACSIN1/syndapin1. Nature Neurosci. 9, 611–621 (2006).

    Article  CAS  PubMed  Google Scholar 

  145. Hayashi, M. et al. Cell- and stimulus-dependent heterogeneity of synaptic vesicle endocytic recycling mechanisms revealed by studies of dynamin 1-null neurons. Proc. Natl Acad. Sci. USA 105, 2175–2180 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Clayton, E. L. et al. The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk endocytosis of synaptic vesicles. J. Neurosci. 29, 7706–7717 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Zuchner, S. et al. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot–Marie–Tooth disease. Nature Genet. 37, 289–294 (2005).

    Article  PubMed  CAS  Google Scholar 

  148. Bitoun, M. et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nature Genet. 37, 1207–1209 (2005).

    Article  CAS  PubMed  Google Scholar 

  149. Durieux, A. C., Prudhon, B., Guicheney, P. & Bitoun, M. Dynamin 2 and human diseases. J. Mol. Med. 88, 339–350 (2010).

    Article  PubMed  Google Scholar 

  150. Nicot, A. S. et al. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nature Genet. 39, 1134–1139 (2007).

    Article  CAS  PubMed  Google Scholar 

  151. Lee, E. et al. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 297, 1193–1196 (2002).

    Article  CAS  PubMed  Google Scholar 

  152. Boumil, R. M. et al. A missense mutation in a highly conserved alternate exon of dynamin-1 causes epilepsy in fitful mice. PLoS Genet. 6, e1001046 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Di Paolo, G. et al. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33, 789–804 (2002).

    Article  CAS  PubMed  Google Scholar 

  154. Koch, D. et al. Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I. EMBO J. 30, 4955–4969 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Milosevic, I. et al. Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission. Neuron 72, 587–601 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Fassio, A. et al. SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function. Hum. Mol. Genet. 20, 2297–2307 (2011).

    Article  CAS  PubMed  Google Scholar 

  157. Patterson, E. E. et al. A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse. Nature Genet. 40, 1235–1239 (2008).

    Article  CAS  PubMed  Google Scholar 

  158. Donaldson, J. G. & Jackson, C. L. ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nature Rev. Mol. Cell Biol. 12, 362–375 (2011).

    Article  CAS  Google Scholar 

  159. Detmer, S. A. & Chan, D. C. Functions and dysfunctions of mitochondrial dynamics. Nature Rev. Mol. Cell Biol. 8, 870–879 (2007).

    Article  CAS  Google Scholar 

  160. Hoppins, S., Lackner, L. & Nunnari, J. The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76, 751–780 (2007).

    Article  CAS  PubMed  Google Scholar 

  161. Okamoto, K. & Shaw, J. M. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu. Rev. Genet. 39, 503–536 (2005).

    Article  CAS  PubMed  Google Scholar 

  162. Westermann, B. Mitochondrial fusion and fission in cell life and death. Nature Rev. Mol. Cell Biol. 11, 872–884 (2010).

    Article  CAS  Google Scholar 

  163. Eppinga, R. D. et al. Increased expression of the large GTPase dynamin 2 potentiates metastatic migration and invasion of pancreatic ductal carcinoma. Oncogene 15 Aug 2011 (doi:10.1038/onc.2011.329).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Hollingworth, P. et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature Genet. 43, 429–435 (2011).

    Article  CAS  PubMed  Google Scholar 

  165. Naj, A. C. et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nature Genet. 43, 436–441 (2011).

    Article  CAS  PubMed  Google Scholar 

  166. Veiga, E. et al. Invasive and adherent bacterial pathogens co-opt host clathrin for infection. Cell Host Microbe 2, 340–351 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Hu, J. et al. A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell 138, 549–561 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Orso, G. et al. Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin. Nature 460, 978–983 (2009).

    Article  CAS  PubMed  Google Scholar 

  169. Haller, O., Gao, S., von der Malsburg, A., Daumke, O. & Kochs, G. Dynamin-like MxA GTPase: structural insights into oligomerization and implications for antiviral activity. J. Biol. Chem 285, 28419–28424 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Prakash, B., Praefcke, G. J., Renault, L., Wittinghofer, A. & Herrmann, C. Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature 403, 567–571 (2000).

    Article  CAS  PubMed  Google Scholar 

  171. Gu, X. & Verma, D. P. Phragmoplastin, a dynamin-like protein associated with cell plate formation in plants. EMBO J. 15, 695–704 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Low, H. H., Sachse, C., Amos, L. A. & Lowe, J. Structure of a bacterial dynamin-like protein lipid tube provides a mechanism for assembly and membrane curving. Cell 139, 1342–1352 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Miyagishima, S. Y. et al. A plant-specific dynamin-related protein forms a ring at the chloroplast division site. Plant Cell 15, 655–665 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Daumke, O. et al. Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling. Nature 449, 923–927 (2007).

    Article  CAS  PubMed  Google Scholar 

  175. Delettre, C. et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nature Genet. 26, 207–210 (2000).

    Article  CAS  PubMed  Google Scholar 

  176. Zuchner, S. et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot–Marie–Tooth neuropathy type 2A. Nature Genet. 36, 449–451 (2004).

    Article  PubMed  CAS  Google Scholar 

  177. Zhao, X. et al. Mutations in a newly identified GTPase gene cause autosomal dominant hereditary spastic paraplegia. Nature Genet. 29, 326–331 (2001).

    Article  CAS  PubMed  Google Scholar 

  178. Waterham, H. R. et al. A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med. 356, 1736–1741 (2007).

    Article  CAS  PubMed  Google Scholar 

  179. Baumgart, T., Capraro, B. R., Zhu, C. & Das, S. L. Thermodynamics and mechanics of membrane curvature generation and sensing by proteins and lipids. Annu. Rev. Phys. Chem. 62, 483–506 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Farsad, K. & De Camilli, P. Mechanisms of membrane deformation. Curr. Opin. Cell Biol. 15, 372–381 (2003).

    Article  CAS  PubMed  Google Scholar 

  181. Antonny, B. Membrane deformation by protein coats. Curr. Opin. Cell Biol. 18, 386–394 (2006).

    Article  CAS  PubMed  Google Scholar 

  182. McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005).

    Article  CAS  PubMed  Google Scholar 

  183. Peter, B. J. et al. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303, 495–499 (2004).

    Article  CAS  PubMed  Google Scholar 

  184. Frost, A. et al. Structural basis of membrane invagination by F-BAR domains. Cell 132, 807–817 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Shimada, A. et al. Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell 129, 761–772 (2007).

    Article  CAS  PubMed  Google Scholar 

  186. Wang, Q. et al. Molecular mechanism of membrane constriction and tubulation mediated by the F-BAR protein pacsin/syndapin. Proc. Natl Acad. Sci. USA 106, 12700–12705 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Rao, Y. et al. Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation. Proc. Natl Acad. Sci. USA 107, 8213–8218 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Cipolat, S., Martins de Brito, O., Dal Zilio, B. & Scorrano, L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc. Natl Acad. Sci. USA 101, 15927–15932 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Moss, T. J., Daga, A. & McNew, J. A. Fusing a lasting relationship between ER tubules. Trends Cell Biol. 21, 416–423 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Gao, S. et al. Structure of myxovirus resistance protein a reveals intra- and intermolecular domain interactions required for the antiviral function. Immunity 35, 514–525 (2011).

    Article  CAS  PubMed  Google Scholar 

  191. Kim, B. H. et al. A family of IFN-γ–inducible 65-kD GTPases protects against bacterial infection. Science 332, 717–721 (2011).

    Article  CAS  PubMed  Google Scholar 

  192. MacMicking, J. D. IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunol. 25, 601–609 (2004).

    Article  CAS  PubMed  Google Scholar 

  193. Gao, H., Kadirjan-Kalbach, D., Froehlich, J. E. & Osteryoung, K. W. ARC5, a cytosolic dynamin-like protein from plants, is part of the chloroplast division machinery. Proc. Natl Acad. Sci. USA 100, 4328–4333 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Glynn, J. M., Miyagishima, S. Y., Yoder, D. W., Osteryoung, K. W. & Vitha, S. Chloroplast division. Traffic 8, 451–461 (2007).

    Article  CAS  PubMed  Google Scholar 

  195. Vater, C. A., Raymond, C. K., Ekena, K., Howald-Stevenson, I. & Stevens, T. H. The VPS1 protein, a homolog of dynamin required for vacuolar protein sorting in Saccharomyces cerevisiae, is a GTPase with two functionally separable domains. J. Cell Biol. 119, 773–786 (1992).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the Howard Hughes Medical Institute, the G. Harold and Leila Y. Mathers Charitable Foundation, US National Institutes of Health grants (R37NS036251, DK45735 and DA018343), the W. M. Keck Foundation and a National Alliance for Research on Schizophrenia and Depression distinguished investigator award to P.D.C. We thank H. Shen, M. Pirucello, A. Raimondi and O. Daumke for their suggestions and insights and M. Pirucello and A. Raimondi for assistance with the preparation of figures.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Related links

Related links

DATABASES

Protein Data Bank

3SNH

FURTHER INFORMATION

Pietro De Camilli's homepage

Glossary

Synaptic vesicles

Small (40 nm in diameter) vesicles within neuronal presynaptic terminals that store and release neurotransmitter.

SRC homology 3 domain

(SH3 domain). A domain that mediates protein–protein interactions and binds Pro-containing short amino acid motifs. This domain is frequently found in proteins involved in signalling, endocytosis and actin regulation.

GAPs and GEFs

(GTPase-activating proteins and guanine nucleotide exchange factors). GAPs promote GTP hydrolysis by GTPases, whereas GEFs displace the GDP generated by the reaction, thus allowing the next cycle of GTP binding and hydrolysis to proceed.

Pleckstrin homology domain

(PH domain). These domains often contain binding sites for phosphoinositides (most typically phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate) and thus help target proteins to specific membranes. However, they can also function in protein–protein interactions.

Line tension

A force that acts to minimize the length of the energetically unfavourable interface between adjacent membrane domains of different composition.

Caveolae

Small flask-shaped invaginations of the plasma membrane that are involved in the endocytic uptake of various cell surface molecules and some viruses, in signalling and in the regulation of plasma membrane tension.

Lamellipodia

Broad, thin plasma membrane protrusions that are driven by actin polymerization and are critical for cell motility and for some forms of bulk endocytosis.

Podosomes

Focal sites of dynamic actin polymerization at the plasma membrane that are found in motile cells at sites of cell–matrix interaction, where they promote the local degradation of the matrix. These structures are critical for supporting cell migration through the extracellular matrix and for bone resorption by osteoclasts. Similar to invadopodia, which are found in invasive cells.

Actin comets

'Tails' of filamentous actin nucleated by endosomes or intracellular pathogens that propel the endosome or pathogen through the cytoplasm through the force produced by actin polymerization.

Calyx of Held

A large synapse within the mammalian auditory brainstem that is suitable (in miceand rats) for presynaptic measurement of membrane capacitance and thus for the detection of synaptic vesicle exocytosis and endocytosis on a millisecond timescale.

Dendritic spines

Small (1 μm), spine-like, actin-rich protrusions of neuronal dendrites that function as postsynaptic sites for excitatory neurotransmission. They are closely opposed to presynaptic sites of neurotransmitter release and are enriched in neurotransmitter receptors.

Charcot–Marie–Tooth disease

A peripheral nervous system dysfunction that is characterized by slow action potential conduction owing to defects in either the myelin sheath, which insulates neuronal axons, or the axons themselves.

Centronuclear myopathy

A group of skeletal muscle diseases that result in muscle weakness and which are characterized by the abnormal central location of nuclei within muscle fibres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferguson, S., De Camilli, P. Dynamin, a membrane-remodelling GTPase. Nat Rev Mol Cell Biol 13, 75–88 (2012). https://doi.org/10.1038/nrm3266

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm3266

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing