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Nat Cell Biol. 2015 Jun;17(6):726-35. doi: 10.1038/ncb3168. Epub 2015 May 4.

An instructive role for C. elegans E-cadherin in translating cell contact cues into cortical polarity.

Author information

1
Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, New York 10016, USA.
2
1] Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, New York 10016, USA [2] Department of Cell Biology, NYU School of Medicine, New York, New York 10016, USA.

Abstract

Cell contacts provide spatial cues that polarize early embryos and epithelial cells. The homophilic adhesion protein E-cadherin is required for contact-induced polarity in many cells. However, it is debated whether E-cadherin functions instructively as a spatial cue, or permissively by ensuring adequate adhesion so that cells can sense other contact signals. In Caenorhabditis elegans, contacts polarize early embryonic cells by recruiting the RhoGAP PAC-1 to the adjacent cortex, inducing PAR protein asymmetry. Here we show that the E-cadherin HMR-1, which is dispensable for adhesion, functions together with the α-catenin HMP-1, the p120 catenin JAC-1, and the previously uncharacterized linker PICC-1 (human CCDC85A-C) to bind PAC-1 and recruit it to contacts. Mislocalizing the HMR-1 intracellular domain to contact-free surfaces draws PAC-1 to these sites and depolarizes cells, demonstrating an instructive role for HMR-1 in polarization. Our findings identify an E-cadherin-mediated pathway that translates cell contacts into cortical polarity by directly recruiting a symmetry-breaking factor to the adjacent cortex.

PMID:
25938815
PMCID:
PMC4449804
DOI:
10.1038/ncb3168
[Indexed for MEDLINE]
Free PMC Article
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