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dc.contributor.authorZheng, Zhen
dc.contributor.authorZhu, Huabin
dc.contributor.authorWan, Qingwen
dc.contributor.authorLiu, Jing
dc.contributor.authorXiao, Zhuoni
dc.contributor.authorSiderovski, David P.
dc.contributor.authorDu, Quansheng
dc.date.accessioned2012-10-26T16:26:47Z
dc.date.available2012-10-26T16:26:47Z
dc.date.issued2010-04-19en_US
dc.identifier.citationJ Cell Biol. 2010 Apr 19; 189(2):275-288en_US
dc.identifier.issn1540-8140en_US
dc.identifier.pmid20385777en_US
dc.identifier.doi10.1083/jcb.200910021en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/582
dc.description.abstractCoordinated cell polarization and mitotic spindle orientation are thought to be important for epithelial morphogenesis. Whether spindle orientation is indeed linked to epithelial morphogenesis and how it is controlled at the molecular level is still unknown. Here, we show that the NuMA- and Ga-binding protein LGN is required for directing spindle orientation during cystogenesis of MDCK cells. LGN localizes to the lateral cell cortex, and is excluded from the apical cell cortex of dividing cells. Depleting LGN, preventing its cortical localization, or disrupting its interaction with endogenous NuMA or Ga proteins all lead to spindle misorientation and abnormal cystogenesis. Moreover, artificial mistargeting of endogenous LGN to the apical membrane results in a near 90° rotation of the spindle axis and profound cystogenesis defects that are dependent on cell division. The normal apical exclusion of LGN during mitosis appears to be mediated by atypical PKC. Thus, cell polarizationâ mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis.
dc.rights© 2010 Zheng et al.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Divisionen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Polarityen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshDogsen_US
dc.subject.meshEpithelial Cellsen_US
dc.subject.meshEpitheliumen_US
dc.subject.meshGTP-Binding Protein alpha Subunitsen_US
dc.subject.meshGene Knockdown Techniquesen_US
dc.subject.meshGenetic Vectorsen_US
dc.subject.meshIntracellular Signaling Peptides and Proteinsen_US
dc.subject.meshLentivirusen_US
dc.subject.meshMembrane Glycoproteinsen_US
dc.subject.meshMitotic Spindle Apparatusen_US
dc.subject.meshMorphogenesisen_US
dc.subject.meshNuclear Matrix-Associated Proteinsen_US
dc.subject.meshProtein Kinase Cen_US
dc.titleLGN regulates mitotic spindle orientation during epithelial morphogenesisen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2856901en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics
dc.contributor.corporatenameDepartment of Neurology
refterms.dateFOA2019-04-09T21:46:11Z
html.description.abstractCoordinated cell polarization and mitotic spindle orientation are thought to be important for epithelial morphogenesis. Whether spindle orientation is indeed linked to epithelial morphogenesis and how it is controlled at the molecular level is still unknown. Here, we show that the NuMA- and Ga-binding protein LGN is required for directing spindle orientation during cystogenesis of MDCK cells. LGN localizes to the lateral cell cortex, and is excluded from the apical cell cortex of dividing cells. Depleting LGN, preventing its cortical localization, or disrupting its interaction with endogenous NuMA or Ga proteins all lead to spindle misorientation and abnormal cystogenesis. Moreover, artificial mistargeting of endogenous LGN to the apical membrane results in a near 90° rotation of the spindle axis and profound cystogenesis defects that are dependent on cell division. The normal apical exclusion of LGN during mitosis appears to be mediated by atypical PKC. Thus, cell polarizationâ mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis.


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