IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Rab27a controls HIV-1 1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate
Autor/es:
PEREYRA GERBER, PEHUEN; CABRINI, MERCEDES; JANCIC, CAROLINA; PAOLETTI, LUCIANA; BANCHIO, CLAUDIA; VON BILDERLING, CATALINA; SIGAUT, LORENA; PIETRASANTA, LIA I.; DUETTE, GABRIEL; FREED, ERIC O.; DE SAINT BASILE, GENEVIEVE; FERREIRA MOITA, CATARINA; FERREIRA MOITA, LUIS; AMIGORENA, SEBASTIAN; BENAROCH, PHILIPPE; JORGE GEFFNER; OSTROWSKI, MATIAS
Revista:
JOURNAL OF CELL BIOLOGY
Editorial:
ROCKEFELLER UNIV PRESS
Referencias:
Lugar: New York; Año: 2015 vol. 209 p. 435 - 452
ISSN:
0021-9525
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 phosphatidylinositol4,5-bisphosphate [PI(4,5)P2] and directs HIV-1 assembly. We show that Rab27a controls 47 the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 alpha PI4KII) towards 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 52 with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KII to the PM. We conclude that by directing the trafficking of PI4KII-positive endosomes towards the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication.