info:eu-repo/semantics/article
Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate
Fecha
2015-02Registro en:
Pereyra Gerber, Federico Pehuén; Cabrini, Mercedes; Jancic, Carolina Cristina; Paoletti, Luciana Elisa; Banchio, Claudia Elena; et al.; Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate; Rockefeller University Press; Journal of Cell Biology; 209; 3; 2-2015; 435-452
0021-9525
CONICET Digital
CONICET
Autor
Pereyra Gerber, Federico Pehuén
Cabrini, Mercedes
Jancic, Carolina Cristina
Paoletti, Luciana Elisa
Banchio, Claudia Elena
Von Bilderling, Catalina
Sigaut, Lorena
Pietrasanta, Lia
Duette, Gabriel
Freed, Eric O.
Basile, Genevieve de Saint
Moita, Catarina Ferreira
Moita, Luis Ferreira
Amigorena, Sebastian
Benaroch, Philippe
Geffner, Jorge Raúl
Ostrowski, Matias
Resumen
During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55Gag membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication.