期刊
MOLECULAR CELL
卷 36, 期 3, 页码 525-535出版社
CELL PRESS
DOI: 10.1016/j.molcel.2009.10.025
关键词
-
资金
- National Institutes of Health [CA82258, RR022232, GM062583]
- American Heart Association [0735252N]
Modulation of actin dynamics through the N-WASp/Arp2/3 pathway is important in cell locomotion, membrane trafficking, and pathogen infection. Here, we demonstrate that Nck is essential for actin remodeling stimulated by phosphatidylinositol 4,5 bisphosphate (PI(4,5)P-2) and, conversely, that PI(4,5)P-2 is necessary for localized actin polymerization induced by Nck in vivo. Nck knockdown or knockout suppressed actin comets induced by phosphatidylinositol 5-kinase (PIP5K), and PIP5K stimulated tyrosine phosphorylation of an Nck SH2 domain binding partner, suggesting that Nck couples phosphotyrosine-and phosphoinositide-dependent signals. We show that PI(4,5)P-2 and PIP35K are both enriched at actin comets induced by Nck aggregates and that formation of actin comets was strongly inhibited by coclustering with an inositol 5-phosphatase domain to decrease local PI(4,5)P-2 levels. The extent of Nck-induced actin polymerization was also modulated by PI(4,5)P-2-sensitive N-WASp mutants. This study uncovers a strong reciprocal interdependence between Nck and PI(4,5)P-2 in promoting localized N-WASp-mediated actin polymerization in cells.
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