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Wdpcp,a PCP Protein Required for Ciliogenesis,Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton
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نویسنده
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cui c. ,chatterjee b. ,lozito t.p. ,zhang z. ,francis r.j. ,yagi h. ,swanhart l.m. ,sanker s. ,francis d. ,yu q. ,san agustin j.t. ,puligilla c. ,chatterjee t. ,tansey t. ,liu x. ,kelley m.w. ,spiliotis e.t. ,kwiatkowski a.v. ,tuan r. ,pazour g.j. ,hukriede n.a. ,lo c.w.
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منبع
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plos biology - 2013 - دوره : 11 - شماره : 11
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چکیده
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Planar cell polarity (pcp) regulates cell alignment required for collective cell movement during embryonic development. this requires pcp/pcp effector proteins,some of which also play essential roles in ciliogenesis,highlighting the long-standing question of the role of the cilium in pcp. wdpcp,a pcp effector,was recently shown to regulate both ciliogenesis and collective cell movement,but the underlying mechanism is unknown. here we show wdpcp can regulate pcp by direct modulation of the actin cytoskeleton. these studies were made possible by recovery of a wdpcp mutant mouse model. wdpcp-deficient mice exhibit phenotypes reminiscent of bardet-biedl/meckel-gruber ciliopathy syndromes,including cardiac outflow tract and cochlea defects associated with pcp perturbation. we observed wdpcp is localized to the transition zone,and in wdpcp-deficient cells,sept2,nphp1,and mks1 were lost from the transition zone,indicating wdpcp is required for recruitment of proteins essential for ciliogenesis. wdpcp is also found in the cytoplasm,where it is localized in the actin cytoskeleton and in focal adhesions. wdpcp interacts with sept2 and is colocalized with sept2 in actin filaments,but in wdpcp-deficient cells,sept2 was lost from the actin cytoskeleton,suggesting wdpcp is required for sept2 recruitment to actin filaments. significantly,organization of the actin filaments and focal contacts were markedly changed in wdpcp-deficient cells. this was associated with decreased membrane ruffling,failure to establish cell polarity,and loss of directional cell migration. these results suggest the pcp defects in wdpcp mutants are not caused by loss of cilia,but by direct disruption of the actin cytoskeleton. consistent with this,wdpcp mutant cochlea has normal kinocilia and yet exhibits pcp defects. together,these findings provide the first evidence,to our knowledge,that a pcp component required for ciliogenesis can directly modulate the actin cytoskeleton to regulate cell polarity and directional cell migration.
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آدرس
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department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa,united states,laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa,united states,laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, center for cellular and molecular engineering,department of orthopedic surgery,university of pittsburgh school of medicine,pittsburgh,pa, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa,united states,laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa,united states,department of biology,canisius college,buffalo,ny, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa, United States, laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, program in molecular medicine,university of massachusetts medical center,worcester,ma, United States, section on developmental neuroscience,national institute on deafness and other communication disorders,national institutes of health,bethesda,md,united states,department of pathology and laboratory medicine,medical university of south carolina,charleston,sc, United States, laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa, United States, section on developmental neuroscience,national institute on deafness and other communication disorders,national institutes of health,bethesda,md, United States, department of biology,drexel university,philadelphia,pa, United States, department of cell biology,university of pittsburgh school of medicine,pittsburgh,pa, United States, center for cellular and molecular engineering,department of orthopedic surgery,university of pittsburgh school of medicine,pittsburgh,pa, United States, program in molecular medicine,university of massachusetts medical center,worcester,ma, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa, United States, department of developmental biology,university of pittsburgh school of medicine,pittsburgh,pa,united states,laboratory of developmental biology,national heart lung and blood institute,national institutes of health,bethesda,md, United States
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Authors
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