Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1

摘要: PtdIns5P is a lipid messenger acting as stress-response mediator in the nucleus, and known to maintain cell activation through traffic alterations upon bacterial infection. Here, we show that regulates actin dynamics invasion via recruitment of exchange factor Tiam1 Rac1. Restricted Rac1 results from binding DH-PH domains PtdIns5P. Using an assay mimics membrane anchoring by using Rac1-His liposomes containing Ni(2+)-NTA modified lipids, demonstrate intrinsic activity increases when anchored PtdIns5P-enriched environment. This pathway appears be general since it valid different pathophysiological models: receptor tyrosine kinase activation, phosphatase IpgD expression invasive NPM-ALK(+) lymphomas. The discovery could keystone GTPases cytoskeleton spatiotemporal regulation opens important research avenues towards unravelling new strategies counteracting invasion.