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Cingulin and actin mediate midbody-dependent apical lumen formation during polarization of epithelial cells

Anthony J. Mangan, Daniel V. Sietsema, Dongying Li, Jeffrey K. Moore, Sandra Citi and Rytis Prekeris ()
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Anthony J. Mangan: School of Medicine, Anschutz Medical Campus, University of Colorado Denver
Daniel V. Sietsema: School of Medicine, Anschutz Medical Campus, University of Colorado Denver
Dongying Li: School of Medicine, Anschutz Medical Campus, University of Colorado Denver
Jeffrey K. Moore: School of Medicine, Anschutz Medical Campus, University of Colorado Denver
Sandra Citi: University of Geneva
Rytis Prekeris: School of Medicine, Anschutz Medical Campus, University of Colorado Denver

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Coordinated polarization of epithelial cells is a key step during morphogenesis that leads to the formation of an apical lumen. Rab11 and its interacting protein FIP5 are necessary for the targeting of apical endosomes to the midbody and apical membrane initiation site (AMIS) during lumenogenesis. However, the machinery that mediates AMIS establishment and FIP5-endosome targeting remains unknown. Here we identify a FIP5-interacting protein, Cingulin, which localizes to the AMIS and functions as a tether mediating FIP5-endosome targeting. We analysed the machinery mediating AMIS recruitment to the midbody and determined that both branched actin and microtubules are required for establishing the site of the nascent lumen. We demonstrate that the Rac1-WAVE/Scar complex mediates Cingulin recruitment to the AMIS by inducing branched actin formation, and that Cingulin directly binds to microtubule C-terminal tails through electrostatic interactions. We propose a new mechanism for apical endosome targeting and AMIS formation around the midbody during epithelial lumenogenesis.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12426

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DOI: 10.1038/ncomms12426

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