학술논문
Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate
Document Type
Author abstract
Author
Gerber, Pehuen Pereyra; Cabrini, Mercedes; Jancic, Carolina; Paoletti, Luciana; Banchio, Claudia; von Bilderling, Catalina; Sigaut, Lorena; Pietrasanta, Lia I.; Duette, Gabriel; Freed, Eric O.; Basile, Genevieve de Saint; Moita, Catarina Ferreira; Moita, Luis Ferreira; Amigorena, Sebastian; Benaroch, Philippe; Geffner, Jorge; Ostrowski, Matias
Source
The Journal of Cell Biology. May 11, 2015, Vol. 209 Issue 3, p435, 18 p.
Subject
Language
English
ISSN
0021-9525
Abstract
During the late stages of the HIV-1 replication cycle, the viral polyprotein [Pr55.sup.Gag] is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)[P.sub.2] ) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 [alpha] (PI4KII[alpha]) toward the PM of CD[4.sup.+] T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)[P.sub.2], therefore controlling [Pr55.sup.Gag] membrane association. Rab27a also controls PI(4,5)[P.sub.2] 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 [Pr55.sup.Gag] with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KII[alpha] to the PM. We conclude that by directing the trafficking of P14KII[alpha]-positive endosomes toward the PM, Rab27a controls PI(4,5)[P.sub.2] production and, consequently, HIV-1 replication. www.jcb.org/cgi/doi/10.1083/jcb.201409082