Submitted February 26, 2008
Accepted December 1, 2008
CD4 - CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface
Lamia Achour, Mark G.H. Scott, Hamasseh Shirvani, Alain Thuret, Georges Bismuth, Catherine Labbe-Jullie, and Stefano Marullo*
Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France
INSERM, U567, Paris, France
* Corresponding author; email: stefano.marullo{at}inserm.fr.
The association of CD4, a glycoprotein involved in T cell development and antigen recognition, and CCR5, a chemotactic G protein-coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for the human immunodeficiency virus HIV. We observed that the vast majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relative low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration-dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cell distribution of CXCR4, the other HIV co-receptor. These results reveal a previously unappreciated role of CD4, which contributes to regulate CCR5 export to the plasma membrane.
