![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 56, Issue 4, 728-736, October 1999
Department of Pharmacology, The University of Iowa, Iowa City, Iowa
The rat lutropin/choriogonadotropin receptor (rLHR) is a member
of the rhodopsin-like subfamily of G protein-coupled receptors that has
two adjacent dileucine motifs in the C-terminal cytoplasmic tail. Here
we show that simultaneous (L613,614,615,616A) or individual (L613,L614A
or L615,616A) mutation of the two adjacent dileucine motifs to alanines
results in mutants with enhanced rates of agonist-induced internalization. The L613,L614A mutation was much more effective in
enhancing internalization than the L615,L616A mutation. Moreover, the
L613A mutation was more effective than the L614A mutation. Because in
the human LHR the residues equivalent to L613 and L614 of the rLHR are
a phenylalanine and a leucine (F635 and L636), we also prepared mutants
that exchanged these motifs. In the rLHR, an LL-to-FL exchange enhanced
endocytosis, and in the human LHR, an FL-to-LL exchange impaired
endocytosis. The internalization of rLHR-wt and rLRH-L613,L614A was
inhibited by coexpression of the clathrin-binding domain of
-arrestin. In fact, this manipulation reduced the enhanced rate of
internalization of rLHR-L613,614A back to that of rLHR-wt. The
L613,614A mutation does not affect the degradation of the internalized
agonist or the membrane targeting of the nascent rLHR. The L615,616A
mutation also did not affect degradation of the internalized agonist
but impaired the membrane targeting of the nascent rLHR. We conclude
that the dileucine-based motifs of the rLHR inhibit internalization and
suggest that this inhibition may be due to an impairment in the binding
of the rLHR to endogenous nonvisual arrestins.
This article has been cited by other articles:
|
|
 |
|
  C. Galet and M. Ascoli A Constitutively Active Mutant of the Human Lutropin Receptor (hLHR-L457R) Escapes Lysosomal Targeting and Degradation Mol. Endocrinol., November 1, 2006; 20(11): 2931 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kuwasako, Y.-N. Cao, C.-P. Chu, S. Iwatsubo, T. Eto, and K. Kitamura Functions of the Cytoplasmic Tails of the Human Receptor Activity-modifying Protein Components of Calcitonin Gene-related Peptide and Adrenomedullin Receptors J. Biol. Chem., March 17, 2006; 281(11): 7205 - 7213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yamashita, K. Nakamura, Y. Omori, K. Tsunekawa, M. Murakami, and T. Minegishi Association of Human Follitropin (FSH) Receptor with Splicing Variant of Human Lutropin/Choriogonadotropin Receptor Negatively Controls the Expression of Human FSH Receptor Mol. Endocrinol., August 1, 2005; 19(8): 2099 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Munshi, C. L. Clouser, H. Peegel, and K. M. J. Menon Evidence that Palmitoylation of Carboxyl Terminus Cysteine Residues of the Human Luteinizing Hormone Receptor Regulates Postendocytic Processing Mol. Endocrinol., March 1, 2005; 19(3): 749 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakamura, S. Yamashita, Y. Omori, and T. Minegishi A Splice Variant of the Human Luteinizing Hormone (LH) Receptor Modulates the Expression of Wild-Type Human LH Receptor Mol. Endocrinol., June 1, 2004; 18(6): 1461 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Galet, T. Hirakawa, and M. Ascoli The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine Mol. Endocrinol., February 1, 2004; 18(2): 434 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hirakawa, C. Galet, M. Kishi, and M. Ascoli GIPC Binds to the Human Lutropin Receptor (hLHR) through an Unusual PDZ Domain Binding Motif, and It Regulates the Sorting of the Internalized Human Choriogonadotropin and the Density of Cell Surface hLHR J. Biol. Chem., December 5, 2003; 278(49): 49348 - 49357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, H. H. Loh, and P.-Y. Law The Intracellular Trafficking of Opioid Receptors Directed by Carboxyl Tail and a Di-leucine Motif in Neuro2A Cells J. Biol. Chem., September 19, 2003; 278(38): 36848 - 36858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. VanLeeuwen, M. E. Steffey, C. Donahue, G. Ho, and R. G. MacKenzie Cell Surface Expression of the Melanocortin-4 Receptor Is Dependent on a C-terminal Di-isoleucine Sequence at Codons 316/317 J. Biol. Chem., April 25, 2003; 278(18): 15935 - 15940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Galet, L. Min, R. Narayanan, M. Kishi, N. L. Weigel, and M. Ascoli Identification of a Transferable Two-Amino-Acid Motif (GT) Present in the C-Terminal Tail of the Human Lutropin Receptor that Redirects Internalized G Protein-Coupled Receptors from a Degradation to a Recycling Pathway Mol. Endocrinol., March 1, 2003; 17(3): 411 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ascoli, F. Fanelli, and D. L. Segaloff The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective Endocr. Rev., April 1, 2002; 23(2): 141 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kishi, X. Liu, T. Hirakawa, D. Reczek, A. Bretscher, and M. Ascoli Identification of Two Distinct Structural Motifs That, When Added to the C-Terminal Tail of the Rat LH Receptor, Redirect the Internalized Hormone-Receptor Complex from a Degradation to a Recycling Pathway Mol. Endocrinol., September 1, 2001; 15(9): 1624 - 1635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. G. Ferguson Evolving Concepts in G Protein-Coupled Receptor Endocytosis: The Role in Receptor Desensitization and Signaling Pharmacol. Rev., March 1, 2001; 53(1): 1 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Min and M. Ascoli Effect of Activating and Inactivating Mutations on the Phosphorylation and Trafficking of the Human Lutropin/Choriogonadotropin Receptor Mol. Endocrinol., November 1, 2000; 14(11): 1797 - 1810. [Abstract] [Full Text]
|
|
|
|
|
|
M. Kishi and M. Ascoli The C-Terminal Tail of the Rat Lutropin/Choriogonadotropin (CG) Receptor Independently Modulates Human (h)CG-Induced Internalization of the Cell Surface Receptor and the Lysosomal Targeting of the Internalized hCG-Receptor Complex Mol. Endocrinol., June 1, 2000; 14(6): 926 - 936. [Abstract] [Full Text]
|
|
|
|
|
|
S. Li, X. Liu, and M. Ascoli p38JAB1 Binds to the Intracellular Precursor of the Lutropin/Choriogonadotropin Receptor and Promotes Its Degradation J. Biol. Chem., April 28, 2000; 275(18): 13386 - 13393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakamura, X. Liu, and M. Ascoli Seven Non-contiguous Intracellular Residues of the Lutropin/Choriogonadotropin Receptor Dictate the Rate of Agonist-induced Internalization and Its Sensitivity to Non-visual Arrestins J. Biol. Chem., January 7, 2000; 275(1): 241 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kishi and M. Ascoli Multiple Distant Amino Acid Residues Present in the Serpentine Region of the Follitropin Receptor Modulate the Rate of Agonist-induced Internalization J. Biol. Chem., September 29, 2000; 275(40): 31030 - 31037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, X. Liu, L. Min, and M. Ascoli Mutations of the Second Extracellular Loop of the Human Lutropin Receptor Emphasize the Importance of Receptor Activation and De-emphasize the Importance of Receptor Phosphorylation in Agonist-induced Internalization J. Biol. Chem., March 9, 2001; 276(11): 7968 - 7973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawakami, F. Takeshita, and R. K. Puri Identification of Distinct Roles for a Dileucine and a Tyrosine Internalization Motif in the Interleukin (IL)-13 Binding Component IL-13 Receptor alpha 2 Chain J. Biol. Chem., June 29, 2001; 276(27): 25114 - 25120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Min, C. Galet, and M. Ascoli The Association of Arrestin-3 with the Human Lutropin/Choriogonadotropin Receptor Depends Mostly on Receptor Activation Rather than on Receptor Phosphorylation J. Biol. Chem., January 4, 2002; 277(1): 702 - 710. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
