The Mammalian Crumbs Complex Defines a Distinct Polarity Domain Apical of Epithelial Tight Junctions.

Current Biology : CB
Benedict TanAlexander Ludwig

Abstract

Epithelial apico-basal polarity is established through the asymmetric cortical distribution of the Par, Crumbs and Scribble polarity modules. Apical (Par and Crumbs) and basolateral (Scribble) polarity modules overlap at the apical-lateral border, which, in mammals, is defined by the apical junctional complex (AJC). The AJC is composed of tight junctions (TJ) and adherens junctions (AJ) and plays fundamental roles in epithelial morphogenesis and plasticity. However, the molecular composition and precise sub-junctional organization of the AJC and its associated polarity regulators are not well defined. Here, we used the peroxidase APEX2 for quantitative proximity proteomics (QPP) and electron microscopy (EM) imaging to dissect the architecture of the AJC in fully polarized MDCK-II cells. We present a high-confidence proteome of the apical-lateral border in which TJ and AJ components and apical and lateral compartment markers are spatially resolved. We further demonstrate that the Crumbs complex (Pals1, PatJ, Lin7c, and Crumbs3) defines a hitherto unidentified membrane compartment apical of TJ, which we coin the vertebrate marginal zone (VMZ). QPP, imaging, and immunoprecipitation assays showed that the HOMER scaffolding proteins...Continue Reading

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Dec 17, 2020·Biomolecules·Soha McheikGilles Freiss
Feb 7, 2021·Cellular and Molecular Gastroenterology and Hepatology·Amy C EngevikJames R Goldenring
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