Filamin-A regulates actin-dependent clustering of HIV receptors
| Autor: | Alfonso Valencia, Antonella Viola, Santos Mañes, Dimiter S. Dimitrov, Lorena Martínez-Prats, Rosa Ana Lacalle, Concepción Gómez-Moutón, Sonia Jiménez-Baranda, Ana M. Rojas, Carlos Martínez-A, Emilia Mira, Rafael Delgado |
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| Přispěvatelé: | Ministerio de Educación y Ciencia (España), Consejo Superior de Investigaciones Científicas (España), European Commission, Instituto de Salud Carlos III, National Cancer Institute (US), Pfizer |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Receptors CXCR4 RHOA Receptors CCR5 viruses Filamins Molecular Sequence Data macromolecular substances Biology HIV Envelope Protein gp120 Filamin Cell Line Contractile Proteins Models Receptors Humans Amino Acid Sequence Cytoskeleton Receptor Actin CXCR4 Microfilament Proteins virus diseases Molecular Cell Biology Cofilin Actin cytoskeleton Actins Cell biology Actin Depolymerizing Factors CD4 Antigens biology.protein HIV-1 Signal transduction rhoA GTP-Binding Protein CCR5 |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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. This work was supported in part by the Spanish Ministry of Education and Science (SAF2005-00241) and the Intramural CSIC Program (PIF 20050F0212) to S.M., the European Union FP6 (INNOCHEM, LSHB-CT-2005-518167) to S.M. and C.M.A., the Instituto de Salud Carlos III (FIS030300; G030173) to R.D., and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research to D.S.D. A.R. is a recipient of MIRG-CT-2005-016499. The Department of Immunology and Oncology was founded and is supported by the Spanish National Research Council (CSIC) and by Pfizer. |
| Databáze: | OpenAIRE |
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