AP-2 complex-mediated endocytosis of Drosophila Crumbs regulates polarity via antagonizing Stardust

Abstract

Maintenance of epithelial polarity depends on the correct localization and levels of polarity determinants. The evolutionarily conserved transmembrane protein Crumbs is crucial for the size and identity of the apical membrane, yet little is known about the molecular mechanisms controlling the amount of Crumbs at the surface. Here, we show that Crumbs levels on the apical membrane depend on a well-balanced state of endocytosis and stabilization. The adaptor protein 2 (AP-2) complex binds to a motif in the cytoplasmic tail of Crumbs that overlaps with the binding site of Stardust, a protein known to stabilize Crumbs on the surface. Preventing endocytosis by mutations in AP-2 causes expansion of the Crumbs-positive plasma membrane and polarity defects, which can be partially rescued by removing one copy of crumbs. Strikingly, knocking-down both AP-2 and Stardust retains Crumbs on the membrane. This study provides evidence for a molecular mechanism, based on stabilization and endocytosis, to adjust surface levels of Crumbs, which are essential for maintaining epithelial polarity.

Publication DOI: https://doi.org/10.1242/jcs.174573
Dataset DOI: https://doi.org/10.17036/0b1a6e26-d052-4106-9d13-d3edbbbb89a6
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: Funding: Max-Planck Society; BBSRC (BB/K014862/1); and Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB). Supplementary information available online at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.174573/-/DC1
Uncontrolled Keywords: AP-2 complex,crumbs,Eendocytosis,epithelial polarity,PDZ-binding,stardust,Cell Biology
Publication ISSN: 1477-9137
Full Text Link: http://jcs.biol ... ent/128/24/4538
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2015-12-15
Published Online Date: 2015-11-02
Accepted Date: 2015-10-26
Submitted Date: 2015-05-15
Authors: Lin, Ya-Huei
Currinn, Heather
Pocha, Shirin Meher
Rothnie, Alice (ORCID Profile 0000-0002-4259-7015)
Wassmer, Thomas
Knust, Elisabeth

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