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Homer3 regulates the establishment of neutrophil polarity

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dc.creator Liu, Shanshan
dc.creator Weiner, Orion D.
dc.creator Kortholt, Arjan
dc.creator Wu, Lani
dc.creator Altschuler, Steven
dc.creator Alkema, W.
dc.creator Fusetti, F.
dc.creator Keizer-Gunnink, A.
dc.creator Pipathsouk, Anne
dc.creator Wu, Julie
dc.date 2015-05-01T00:00:00Z
dc.date.accessioned 2023-01-09T12:03:39Z
dc.date.available 2023-01-09T12:03:39Z
dc.identifier 67a6af34-fc06-413b-a0f8-66fff473812a
dc.identifier 10.1091/mbc.e14-07-1197
dc.identifier https://avesis.sdu.edu.tr/publication/details/67a6af34-fc06-413b-a0f8-66fff473812a/oai
dc.identifier.uri http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/97949
dc.description Most chemoattractants rely on activation of the heterotrimeric G-protein G alpha i to regulate directional cell migration, but few links from G alpha i to chemotactic effectors are known. Through affinity chromatography using primary neutrophil lysate, we identify Homer3 as a novel G alpha 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.
dc.language eng
dc.rights info:eu-repo/semantics/closedAccess
dc.title Homer3 regulates the establishment of neutrophil polarity
dc.type info:eu-repo/semantics/article


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