A reciprocal interdependence between Nck and PI(4,5)P(2) promotes localized N-WASp-mediated actin polymerization in living cells.

Molecular Cell
Gonzalo M RiveraBruce J Mayer

Abstract

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 PIP5K 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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Citations

Sep 20, 2012·Journal of Lipid Research·Akua N RoachGuangwei Du
May 23, 2012·The Journal of Cell Biology·Jonathon A DitlevBruce J Mayer
Nov 27, 2015·Molecular Biology of the Cell·Sofya BorinskayaBruce J Mayer
Aug 13, 2015·Cellular and Molecular Life Sciences : CMLS·Loretta TuostoRicciarda Galandrini
Jul 28, 2013·Bioarchitecture·Sankar P Chaki, Gonzalo M Rivera
Jan 21, 2015·The Journal of Cell Biology·Lawrence L LeClaireDiane L Barber
Jul 12, 2017·Nature Reviews. Immunology·Pavel Tolar
Sep 29, 2017·Molecular Biology of the Cell·David C MorrisGonzalo M Rivera
Feb 26, 2010·Nature Reviews. Immunology·Adrian J Thrasher, Siobhan O Burns
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yosuke SenjuPekka Lappalainen
Apr 12, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Yue SunRichard A Anderson
Dec 30, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michela MuscoliniLoretta Tuosto
Jun 29, 2010·Experimental Cell Research·Shruti Haralalka, Susan M Abmayr
Sep 18, 2012·Cell Host & Microbe·Ashley C HumphriesMichael Way

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