TY - JOUR
T1 - The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry
AU - Gordón-Alonso, Mónica
AU - Rocha-Perugini, Vera
AU - Álvarez, Susana
AU - Moreno-Gonzalo, Olga
AU - Ursa, Ángeles
AU - López-Martín, Soraya
AU - Izquierdo-Useros, Nuria
AU - Martínez-Picado, Javier
AU - Muñoz-Fernández, Maria Ángeles
AU - Yáñez-Mó, María
AU - Sánchez-Madrid, Francisco
PY - 2012/6/15
Y1 - 2012/6/15
N2 - Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4 + T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP 2) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP 2 accumulation is increased in syntenin-1-depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP2 production, and the dynamics of HIV-1 entry. © 2012 Gordón-Alonso et al.
AB - Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4 + T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP 2) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP 2 accumulation is increased in syntenin-1-depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP2 production, and the dynamics of HIV-1 entry. © 2012 Gordón-Alonso et al.
U2 - 10.1091/mbc.E11-12-1003
DO - 10.1091/mbc.E11-12-1003
M3 - Article
VL - 23
SP - 2253
EP - 2263
IS - 12
ER -
