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Filamin-A regulates actin-dependent clustering of HIV receptors
Authors:Jiménez-Baranda Sonia  Gómez-Moutón Concepción  Rojas Ana  Martínez-Prats Lorena  Mira Emilia  Ana Lacalle Rosa  Valencia Alfonso  Dimitrov Dimiter S  Viola Antonella  Delgado Rafael  Martínez-A Carlos  Mañes Santos
Institution:Department of Immunology and Oncology Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain.
Abstract: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 membranes. 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 cytoskeleton. 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.
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