ESCRT Machinery Potentiates HIV-1 Utilization of the PI(4,5)P2-PLC-IP3R-Ca2+ Signaling Cascade

摘要: Abstract Human immunodeficiency virus type 1 (HIV-1) release efficiency is directed by late (L) domain motifs in the viral structural precursor polyprotein Gag, which serve as links to ESCRT ( e ndosomal s orting c omplex r equired for t ransport) machinery. Linkage normally through binding of Tsg101, an ESCRT-1 component, P 7 TAP motif p6 region Gag. In its absence, budding Alix, adaptor protein, LY 36 PX n L We recently showed that requires activation inositol 1,4,5-triphosphate receptor (IP3R), a protein “gates” Ca 2+ from intracellular stores, triggers cell influx and thereby functions major regulator signaling. present study, we determined whether Gag signaling Depletion IP3R inactivation phospholipase C (PLC) inhibited or not Tsg101 was bound PLC hydrolysis phosphatidylinositol-(4,5)-bisphosphate generates (1,4,5)-triphosphate, ligand activates IP3R. However, with bound, independent Gq-mediated PLC, readily enhanced pharmacological stimulation PLC. Moreover, redistributed periphery cytosolic elevated, events indicative induction The results suggest function, machinery are linked release.