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PMID: 20385777 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

LGN regulates mitotic spindle orientation during epithelial morphogenesis.

The Journal of cell biology ·Vol. 189 ·No. 2 ·2010-04-19 ·Pages 275-88

Zheng Z, Zhu H, Wan Q, Liu J, Xiao Z, Siderovski DP, Du Q

Abstract

Coordinated 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 Galpha-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 Galpha proteins all lead to spindle misorientation and abnormal cystogenesis. Moreover, artificial mistargeting of endogenous LGN to the apical membrane results in a near 90 degrees 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 polarization-mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis.

MeSH Terms
Animals Cell Division/physiology Cell Line Cell Polarity Cell Proliferation Dogs Epithelial Cells/cytology,physiology Epithelium/embryology GTP-Binding Protein alpha Subunits/genetics,metabolism Gene Knockdown Techniques Genetic Vectors/genetics,metabolism Intracellular Signaling Peptides and Proteins/genetics,metabolism Lentivirus/genetics,metabolism Membrane Glycoproteins/genetics,metabolism Morphogenesis/physiology Nuclear Matrix-Associated Proteins/genetics,metabolism Protein Kinase C/genetics,metabolism Spindle Apparatus/metabolism,ultrastructure
Chemicals
GTP-Binding Protein alpha Subunits Intracellular Signaling Peptides and Proteins Membrane Glycoproteins Nuclear Matrix-Associated Proteins PKC-3 protein Protein Kinase C
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zheng Zhen
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Zhu Huabin
Wan Qingwen
Liu Jing
Xiao Zhuoni
Siderovski David P
Du Quansheng
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200910021
Published
2010-04-19
Epub
2010-00-12
Pages
275-88
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2856901
Subset
IM
Grants
NIGMS NIH HHS · R01 GM074268 · United States
NIGMS NIH HHS · R01 GM079506 · United States
NIGMS NIH HHS · GM079506 · United States
NIGMS NIH HHS · GM074268 · United States
External Links
PubMed source DOI: 10.1083/jcb.200910021 PMC Full Text View journal details
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