Letter abstract
Nature Cell Biology 9, 838 - 846 (2007)
Published online: 17 June 2007 | doi:10.1038/ncb1610
Filamin-A regulates actin-dependent clustering of HIV receptors
Sonia Jiménez-Baranda1, Concepción Gómez-Moutón1, Ana Rojas2,6, Lorena Martínez-Prats3, Emilia Mira1, Rosa Ana Lacalle1, Alfonso Valencia2,6, Dimiter S. Dimitrov4, Antonella Viola5, Rafael Delgado3, Carlos Martínez-A.1 & Santos Mañes1
Human immunodeficiency virus (HIV)-1 infection requires envelope (Env) glycoprotein gp120-induced clustering of CD4 and coreceptors (CCR5 or CXCR4) on the cell surface; this enables Env gp41 activation and formation of a complex that mediates fusion between Env-containing and target-cell membranes1. Kinetic studies show that viral receptors are actively transported to the Env-receptor interface in a process that depends on plasma membrane composition and the actin cytoskeleton2, 3, 4, 5, 6, 7. The mechanisms by which HIV-1 induces F-actin rearrangement in the target cell remain largely unknown. Here, we show that CD4 and the coreceptors interact with the actin-binding protein filamin-A, whose binding to HIV-1 receptors regulates their clustering on the cell surface. We found that gp120 binding to cell receptors induces transient cofilin-phosphorylation inactivation through a RhoA–ROCK-dependent mechanism. Blockade of filamin-A interaction with CD4 and/or coreceptors inhibits gp120-induced RhoA activation and cofilin inactivation. Our results thus identify filamin-A as an adaptor protein that links HIV-1 receptors to the actin cytoskeleton remodelling machinery, which may facilitate virus infection.
- Department of Immunology and Oncology Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain.
- Bioinformatics Unit, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain.
- Servicio de Microbiología, Hospital 12 de Octubre, Avda. de Córdoba, 28041 Madrid, Spain.
- CCR Nanobiology Program, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702-1201, USA.
- Venetian Institute of Molecular Medicine, University of Padova, 35100 Padua, Italy.
- Current address: Computational and Structural Biology Group, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Correspondence to: Santos Mañes1 e-mail: smanes@cnb.uam.es
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