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10.1091/mbc.E14-07-1197

http://scihub22266oqcxt.onion/10.1091/mbc.E14-07-1197
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suck abstract from ncbi


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pmid25739453
      Mol+Biol+Cell 2015 ; 26 (9 ): 1629-39
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  • Homer3 regulates the establishment of neutrophil polarity #MMPMID25739453
  • Wu J ; Pipathsouk A ; Keizer-Gunnink A ; Fusetti F ; Alkema W ; Liu S ; Altschuler S ; Wu L ; Kortholt A ; Weiner OD
  • Mol Biol Cell 2015[May]; 26 (9 ): 1629-39 PMID25739453 show ga
  • Most chemoattractants rely on activation of the heterotrimeric G-protein G?i to regulate directional cell migration, but few links from G?i to chemotactic effectors are known. Through affinity chromatography using primary neutrophil lysate, we identify Homer3 as a novel G?i2-binding protein. RNA interference-mediated knockdown of Homer3 in neutrophil-like HL-60 cells impairs chemotaxis and the establishment of polarity of phosphatidylinositol 3,4,5-triphosphate (PIP3) and the actin cytoskeleton, as well as the persistence of the WAVE2 complex. Most previously characterized proteins that are required for cell polarity are needed for actin assembly or activation of core chemotactic effectors such as the Rac GTPase. In contrast, Homer3-knockdown cells show normal magnitude and kinetics of chemoattractant-induced activation of phosphoinositide 3-kinase and Rac effectors. Chemoattractant-stimulated Homer3-knockdown cells also exhibit a normal initial magnitude of actin polymerization but fail to polarize actin assembly and intracellular PIP3 and are defective in the initiation of cell polarity and motility. Our data suggest that Homer3 acts as a scaffold that spatially organizes actin assembly to support neutrophil polarity and motility downstream of GPCR activation.
  • |Actin Cytoskeleton/metabolism [MESH]
  • |Carrier Proteins/*physiology [MESH]
  • |Cell Polarity [MESH]
  • |Chemotaxis [MESH]
  • |Gene Expression [MESH]
  • |Gene Knockdown Techniques [MESH]
  • |HL-60 Cells [MESH]
  • |Homer Scaffolding Proteins [MESH]
  • |Humans [MESH]
  • |Neutrophils/*physiology [MESH]
  • |RNA, Small Interfering/genetics [MESH]


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