کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2184790 1095930 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ESCRT Machinery Potentiates HIV-1 Utilization of the PI(4,5)P2-PLC-IP3R-Ca2+ Signaling Cascade
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
ESCRT Machinery Potentiates HIV-1 Utilization of the PI(4,5)P2-PLC-IP3R-Ca2+ Signaling Cascade
چکیده انگلیسی

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 the ESCRT (endosomal sorting complex required for transport) machinery. Linkage is normally through binding of Tsg101, an ESCRT-1 component, to the P7TAP motif in the p6 region of Gag. In its absence, budding is directed by binding of Alix, an ESCRT adaptor protein, to the LY36PXnL motif in Gag. We recently showed that budding requires activation of the inositol 1,4,5-triphosphate receptor (IP3R), a protein that “gates” Ca2+ release from intracellular stores, triggers Ca2+ cell influx and thereby functions as a major regulator of Ca2+ signaling. In the present study, we determined whether the L domain links Gag to Ca2+ signaling machinery. Depletion of IP3R and inactivation of phospholipase C (PLC) inhibited budding whether or not Tsg101 was bound to Gag. PLC hydrolysis of phosphatidylinositol-(4,5)-bisphosphate generates inositol (1,4,5)-triphosphate, the ligand that activates IP3R. However, with Tsg101 bound, Gag release was independent of Gq-mediated activation of PLC, and budding was readily enhanced by pharmacological stimulation of PLC. Moreover, IP3R was redistributed to the cell periphery and cytosolic Ca2+ was elevated, events indicative of induction of Ca2+ signaling. The results suggest that L domain function, ESCRT machinery and Ca2+ signaling are linked events in Gag release.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 413, Issue 2, 21 October 2011, Pages 347–358
نویسندگان
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