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Rab35 GTPase couples cell division with initiation of epithelial apico-basal polarity and lumen opening

Author

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  • Kerstin Klinkert

    (Institut Pasteur
    Centre National de la Recherche Scientifique UMR3691
    Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Institut de formation doctorale)

  • Murielle Rocancourt

    (Institut Pasteur
    Centre National de la Recherche Scientifique UMR3691)

  • Anne Houdusse

    (Institut Curie, Structural Motility Lab)

  • Arnaud Echard

    (Institut Pasteur
    Centre National de la Recherche Scientifique UMR3691)

Abstract

Establishment and maintenance of apico-basal polarity in epithelial organs must be tightly coupled with cell division, but the underlying molecular mechanisms are largely unknown. Using 3D cultures of renal MDCK cells (cysts), we found that the Rab35 GTPase plays a crucial role in polarity initiation and apical lumen positioning during the first cell division of cyst development. At the molecular level, Rab35 physically couples cytokinesis with the initiation of apico-basal polarity by tethering intracellular vesicles containing key apical determinants at the cleavage site. These vesicles transport aPKC, Cdc42, Crumbs3 and the lumen-promoting factor Podocalyxin, and are tethered through a direct interaction between Rab35 and the cytoplasmic tail of Podocalyxin. Consequently, Rab35 inactivation leads to complete inversion of apico-basal polarity in 3D cysts. This novel and unconventional mode of Rab-dependent vesicle targeting provides a simple mechanism for triggering both initiation of apico-basal polarity and lumen opening at the centre of cysts.

Suggested Citation

  • Kerstin Klinkert & Murielle Rocancourt & Anne Houdusse & Arnaud Echard, 2016. "Rab35 GTPase couples cell division with initiation of epithelial apico-basal polarity and lumen opening," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11166
    DOI: 10.1038/ncomms11166
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    Cited by:

    1. Sara Bisi & Stefano Marchesi & Abrar Rizvi & Davide Carra & Galina V. Beznoussenko & Ines Ferrara & Gianluca Deflorian & Alexander Mironov & Giovanni Bertalot & Federica Pisati & Amanda Oldani & Angel, 2020. "IRSp53 controls plasma membrane shape and polarized transport at the nascent lumen in epithelial tubules," Nature Communications, Nature, vol. 11(1), pages 1-23, December.
    2. Caitlin R. Francis & Hayle Kincross & Erich J. Kushner, 2022. "Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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