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The co-workers of actin filaments: from cell structures to signals

Nature Reviews Molecular Cell Biology volume 5, pages 635–646 (2004)Cite this article

Key Points

  • Actin filaments in membrane protrusions are organized either in bundles — as occurs in microvilli, stereocilia and bristles — or in branched networks, as occurs in lamellipodia. Filopodia are distinct from bundle-based structures as they are supported by a bundled bunch of actin filaments that emerge from a pre-existing branched network.

  • The morphology of each type of protrusion is determined by the content of actin-binding proteins (ABPs) as well as their concentration in cells. A wide range of ABPs organizes the networks and specifies their shape, size and location. However, these networks are not static but are the result of a balance between filament polymerization and depolymerization, which is finely regulated by ABPs.

  • The control of the actin cytoskeleton and its remodelling in response to environmental stimuli are the result of a complex regulation of ABPs. They are downstream effectors of several signalling pathways including those induced by phospholipase Cγ1 and the small GTPases. Calcium- and phosphoinositide-binding or phosphorylation are among the molecular cues that modify ABP activities towards actin.

  • The regulation of selected ABPs is illustrated in a selection of dynamic cellular events: gelsolin and actin-depolymerizing factor (ADF)/cofilin, for their role in enhancing actin treadmilling; villin and ezrin/radixin/moesin (ERM) proteins, for the breakdown of structures to generate new specializations; and filamin and fascin, for their regulation in the formation of dynamic protrusions. Finally, the regulation of ABPs is implicated in the establishment of cell defence structures.

  • The integration of the complex regulation of ABPs in the study of microfilament functions is discussed. Post-translational modifications and the many interactions of ABPs have prompted the use of cell-culture and animal models that resemble physiological conditions.

Abstract

Cells have various surface architectures, which allow them to carry out different specialized functions. Actin microfilaments that are associated with the plasma membrane are important for generating these cell-surface specializations, and also provide the driving force for remodelling cell morphology and triggering new cell behaviour when the environment is modified. This phenomenon is achieved through a tight coupling between cell structure and signal transduction, a process that is modulated by the regulation of actin-binding proteins.

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Figure 1: Actin networks in cellular protrusions.
Figure 2: Phosphoinositides and actin filaments.
Figure 3: Model of villin regulation in actin remodelling.
Figure 4: Filamin, fascin and the formation of protrusions.
Figure 5: Regulation of Arp2/3 and cofilin in the formation of immunological synapses.

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Acknowledgements

We sincerely thank J. Srivastava and D. Vignjevic for careful reading of the manuscript and helpful comments. This work was supported by funds from the French ministry of research, Action Concertée Incitative Biologie du développement et physiologie intégrative. C.R. is supported by a Ph.D. fellowship from the Centre National de la Recherche Scientifique and R.A. is supported by a post-doctoral fellowship from the Institut Pasteur.

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  1. UMR144 Centre National de la Recherche Scientifique/Institut Curie, Paris, France

    Céline Revenu, Rafika Athman, Sylvie Robine & Daniel Louvard

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  1. Céline Revenu
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DATABASES

Flybase

Ena

fimbrin

quail

Interpro

ActA

FERM

VCA

Swiss-Prot

ezrin

fascin

filamin A

gelsolin

harmonin b

moesin

myosin VIIa

myosin XVa

NCK

PAK

radixin

SLP76

villin

VASP

VAV

WASP

Glossary

PHAGOCYTOSIS

An actin-dependent process by which cells engulf external particulate material by extension and fusion of pseudopods.

MICROVILLI

Small, finger-like projections (1–2 μm long and 100 nm wide) that occur on the exposed surfaces of epithelial cells to maximize the surface area.

STEREOCILIA

Tapered, finger-like projections from hair cells of the inner ear that respond to mechanical displacement with alterations in membrane potential, and thereby mediate sensory transduction.

FILOPODIA

Thin cellular processes containing long, unbranched, parallel bundles of actin filaments.

LAMELLIPODIA

Broad, flat protrusions at the leading edge of a moving cell that are enriched with a branched network of actin filaments.

SCHWANN CELLS

Supporting cells of the peripheral nervous system that associate with peripheral axons and can contribute to their myelination.

LEADING EDGE

The thin margin of a lamellipodium spanning the area of the cell from the plasma membrane to about 1 μm back into the lamellipodium.

HAIR CELLS

The sensory cells in the organ of Corti from the inner ear.

NURSE-CELL STRUT

D. melanogaster nurse cells are auxiliary cells that supply the oocyte with synthesized mRNAs and proteins during insect oogenesis. Nurse-cell struts are the cytoplasmic actin bundles in these cells that prevent the nucleus from blocking the canals that allow the delivery of cytoplasmic components to the oocyte.

ECTOPLASMIC SPECIALIZATION

An intercellular junction that tightly attaches the elongate spermatid head to the membrane of a Sertoli cell. It is characterized by the presence of a junctional plaque which contains a layer of tightly packed actin bundles under the Sertoli-cell plasma membrane.

SERTOLI CELLS

Non-dividing supporting cells that extend from the base of the seminiferous epithelium to the tubule lumen. They surround germ cells and provide a microenvironment in which germ cells develop and differentiate.

IMMUNOLOGICAL SYNAPSE

A junction that forms at the contact region between a T cell and its target cells. T-cell activation occurs here.

ANTIGEN-PRESENTING CELL

A cell, generally a macrophage or dendritic cell, that presents an antigen to activate a T cell.

GROWTH CONE

Motile tip of the axon or dendrite of a growing nerve cell, which spreads out into a cone-shaped outgrowth.

BILE CANALICULI

Tiny channels on the surface of liver cells that collect the bile that they produce.

MYOSIN

Molecular motors that move along actin filaments and have several cellular roles in contraction or protein transport.

FRAP

(fluorescence recovery after photobleaching). This technique involves the irradiation of a limited region containing fluorescent molecules, such that the fluorescent molecules inside the region become non-fluorescent. The subsequent reappearance of fluorescent molecules from the surrounding non-bleached region gives information on their dynamic parameters such as diffusion coefficient, immobile fraction and binding or residence time.

HAEMOSTATIC RESPONSE

The process that allows platelets to carry out coagulation.

RHO-FAMILY GTPases

Ras-related small GTPases that function as GDP/GTP-regulated binary switches and regulate signal-transduction pathways that control actin organization. RhoGTPase function is required for both the establishment of a fully polarized state and a motile phenotype on epithelial–mesenchymal transition.

MEMBRANE RUFFLES

Processes that are formed by lamellipodia that have lifted from the substratum on which they previously extended.

GLYCOCALYX

The carbohydrate-rich region at the surface of many plant and animal cells that is rich in glycoproteins and glycolipids.

MAJOR HISTOCOMPATIBILITY COMPLEX

A complex of genetic loci in higher vertebrates that encodes a family of cellular antigens that allow the immune system to recognize self from non-self.

ADAPTOR PROTEINS

Proteins that usually have several protein–protein interaction domains and increase cellular responses by recruiting other proteins to a complex.

BRUSH BORDER

The apical surface of epithelial intestinal or kidney cells. It is involved in absorption, and is characterized by the presence of abundant microvilli.

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Revenu, C., Athman, R., Robine, S. et al. The co-workers of actin filaments: from cell structures to signals. Nat Rev Mol Cell Biol 5, 635–646 (2004). https://doi.org/10.1038/nrm1437

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