Hem-1 Complexes Are Essential for Rac Activation, Actin Polymerization, and Myosin Regulation during Neutrophil Chemotaxis

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Hem-1 Complexes Are Essential for Rac Activation, Actin Polymerization, and Myosin Regulation during Neutrophil Chemotaxis

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dc.contributor.author Weiner, Orion D
dc.contributor.author Rentel, Maike C
dc.contributor.author Ott, Alex
dc.contributor.author Bourne, Henry R
dc.contributor.author Schliwa, Manfred
dc.contributor.author Brown, Glenn E.
dc.contributor.author Jedrychowski, Mark P.
dc.contributor.author Yaffe, Michael Bruce
dc.contributor.author Gygi, Steven P.
dc.contributor.author Cantley, Lewis C.
dc.contributor.author Kirschner, Marc W.
dc.date.accessioned 2011-12-23T01:18:54Z
dc.date.issued 2006
dc.identifier.citation Weiner, Orion D, Maike C Rentel, Alex Ott, Glenn E Brown, Mark Jedrychowski, Michael B Yaffe, Steven P Gygi, et al. 2006. Hem-1 Complexes Are Essential for Rac Activation, Actin Polymerization, and Myosin Regulation during Neutrophil Chemotaxis. PLoS Biology 4(2): e38. en_US
dc.identifier.issn 1544-9173 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978614
dc.description.abstract Migrating cells need to make different actin assemblies at the cell's leading and trailing edges and to maintain physical separation of signals for these assemblies. This asymmetric control of activities represents one important form of cell polarity. There are significant gaps in our understanding of the components involved in generating and maintaining polarity during chemotaxis. Here we characterize a family of complexes (which we term leading edge complexes), scaffolded by hematopoietic protein 1 (Hem-1), that organize the neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE)2 complex, which mediates activation of actin polymerization by Rac, is only one member of this family. A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins. RNA interference–mediated knockdown of Hem-1–containing complexes in neutrophil-like cells: (a) dramatically impairs attractant-induced actin polymerization, polarity, and chemotaxis; (b) substantially weakens Rac activation and phosphatidylinositol-(3,4,5)-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5)-tris-phosphate)/Rac/F-actin–mediated feedback circuit that organizes the leading edge; and (c) prevents exclusion of activated myosin from the leading edge, perhaps by misregulating leading edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken together, these observations show that versatile Hem-1–containing complexes coordinate diverse regulatory signals at the leading edge of polarized neutrophils, including but not confined to those involving WAVE2-dependent actin polymerization. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi://10.1371/journal.pbio.0040038 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334198/pdf/ en_US
dash.license LAA
dc.subject eukaryoes en_US
dc.subject biochemistry en_US
dc.subject systems biology en_US
dc.subject cell biology en_US
dc.title Hem-1 Complexes Are Essential for Rac Activation, Actin Polymerization, and Myosin Regulation during Neutrophil Chemotaxis en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Biology en_US
dash.depositing.author Kirschner, Marc W.
dc.date.available 2011-12-23T01:18:54Z
dash.affiliation.other HMS^Cell Biology en_US
dash.affiliation.other HMS^Cell Biology en_US
dash.affiliation.other HMS^Systems Biology en_US
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US
dash.affiliation.other HMS^Systems Biology en_US

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