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Nat Commun. 2014 Jun 6;5:4080. doi: 10.1038/ncomms5080.

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

Author information

1
INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France.
2
INSERM, UMR1043, Plateau Technique D'imagerie Cellulaire, Centre de Physiopathologie de Toulouse Purpan, 31024 Toulouse, France.
3
Institute of Biochemistry and Genetics, University of Basel, Basel 4058, Switzerland.
4
1] INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 31432 Toulouse, France [2] CHU de Toulouse, Laboratoire d'Hématologie, 31059 Toulouse, France.

Abstract

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

PMID:
24905281
DOI:
10.1038/ncomms5080
[Indexed for MEDLINE]

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