MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on September 12, 2007; DOI: 10.1124/mol.107.038422

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.107.038422v1
72/6/1497    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Delhaye, M.
Right arrow Articles by Brelot, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Delhaye, M.
Right arrow Articles by Brelot, A.


Received for publication May 23, 2007.
Revised August 18, 2007.
Accepted for publication September 11, 2007.

Identification of a Post-endocytic Sorting Sequence in CCR5

Maurine Delhaye 1, Audrey Gravot 1, Diana Ayinde 1, Florence Niedergang 1, Marc Alizon 1, Anne Brelot 1*

1 Institut Cochin U567

* Address correspondence to: E-mail: brelot{at}cochin.inserm.fr

Abstract

The chemokine receptor 5 (CCR5), a member of the G protein-coupled receptor family (GPCR), is used by human immunodeficiency virus type 1 (HIV-1) with a R5 tropism as an entry receptor in addition to CD4. It is a key target for an antiviral action aiming at inhibiting the HIV-1 entry process. Only few data are available today regarding the mechanism involved in the intracellular trafficking process of CCR5. Understanding how CCR5 cell surface expression is regulated is particularly important in regards to HIV-1 entry inhibition. We set out to investigate whether CCR5 molecular determinants were involved in the post-endocytic recycling and degradative pathways. We constructed progressive deletion mutants of the C-terminal domain of CCR5 that we stably expressed in HEK293 cells. All of the deletion mutants were expressed at the cell surface and were functional HIV-1 receptors. The deletion mutants were internalized after stimulation, but they lost their ability to recycle to the plasma membrane. They were re-routed towards a lysosomal degradative pathway. We identified here a sequence of 4 amino acids, present at the extreme C-terminus of CCR5, which is necessary for the recycling of the internalized receptor, independently of its phosphorylation. A detailed analysis of this sequence indicated that the 4 amino acids acted as a PDZ interacting sequence. These results show that the CCR5 cytoplasmic domain bears a sequence similar to the "recycling signals" previously identified in other GPCRs. It is likely that drugs able to disrupt the recycling pathway may constitute promising tools for therapeutic treatment.


Key words: Chemotactic peptides, Recycling, Fluorescence techniques, Mutagenesis/Chimeric approaches


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
P. J. Baugher and A. Richmond
The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis
J. Biol. Chem., November 7, 2008; 283(45): 30868 - 30878.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics