LGN regulates mitotic spindle orientation during epithelial morphogenesis

Zhen Zheng, Huabin Zhu, Qingwen Wan, Jing Liu, Zhuoni Xiao, David P. Siderovski, Quansheng Du

Research output: Contribution to journalArticle

124 Citations (Scopus)

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 Gα-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 Gα 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 polarization-mediated spatial restriction of spindle orientation determinants is critical for epithelial morphogenesis.

Original languageEnglish (US)
Pages (from-to)275-288
Number of pages14
JournalJournal of Cell Biology
Volume189
Issue number2
DOIs
StatePublished - Apr 19 2010

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Spindle Apparatus
Morphogenesis
Madin Darby Canine Kidney Cells
GTP-Binding Proteins
Mitosis
Cell Division
Carrier Proteins
Membranes

ASJC Scopus subject areas

  • Cell Biology

Cite this

LGN regulates mitotic spindle orientation during epithelial morphogenesis. / Zheng, Zhen; Zhu, Huabin; Wan, Qingwen; Liu, Jing; Xiao, Zhuoni; Siderovski, David P.; Du, Quansheng.

In: Journal of Cell Biology, Vol. 189, No. 2, 19.04.2010, p. 275-288.

Research output: Contribution to journalArticle

Zheng, Z, Zhu, H, Wan, Q, Liu, J, Xiao, Z, Siderovski, DP & Du, Q 2010, 'LGN regulates mitotic spindle orientation during epithelial morphogenesis', Journal of Cell Biology, vol. 189, no. 2, pp. 275-288. https://doi.org/10.1083/jcb.200910021
Zheng Z, Zhu H, Wan Q, Liu J, Xiao Z, Siderovski DP et al. LGN regulates mitotic spindle orientation during epithelial morphogenesis. Journal of Cell Biology. 2010 Apr 19;189(2):275-288. https://doi.org/10.1083/jcb.200910021
Zheng, Zhen ; Zhu, Huabin ; Wan, Qingwen ; Liu, Jing ; Xiao, Zhuoni ; Siderovski, David P. ; Du, Quansheng. / LGN regulates mitotic spindle orientation during epithelial morphogenesis. In: Journal of Cell Biology. 2010 ; Vol. 189, No. 2. pp. 275-288.
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