Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes.

TitleCelsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes.
Publication TypeJournal Article
Year of Publication2021
AuthorsStahley, SN, Basta, LP, Sharan, R, Devenport, D
JournalElife
Volume10
Date Published2021 Feb 02
ISSN2050-084X
Abstract

To orchestrate collective polarization across tissues, planar cell polarity (PCP) proteins localize asymmetrically to cell junctions, a conserved feature of PCP that requires the atypical cadherin Celsr1. We report that mouse Celsr1 engages in both trans- and cis-interactions, and organizes into dense and highly stable punctate assemblies. We provide evidence suggesting that PCP-mutant variant of Celsr1, Celsr1Crsh, selectively impairs lateral cis-interactions. Although Celsr1Crsh mediates cell adhesion in trans, it displays increased mobility, diminishes junctional enrichment, and fails to engage in homophilic adhesion with the wild-type protein, phenotypes that can be rescued by ectopic cis-dimerization. Using biochemical and super-resolution microscopy approaches, we show that although Celsr1Crsh physically interacts with PCP proteins Frizzled6 and Vangl2, it fails to organize these proteins into asymmetric junctional complexes. Our results suggest mammalian Celsr1 functions not only as a trans-adhesive homodimeric bridge, but also as an organizer of intercellular Frizzled6 and Vangl2 asymmetry through lateral, cis-interactions.

DOI10.7554/eLife.62097
Alternate JournalElife
PubMed ID33529151
PubMed Central IDPMC7857726
Grant ListR01AR068320 / NH / NIH HHS / United States
R01AR066070 / NH / NIH HHS / United States
F32AR071764 / NH / NIH HHS / United States
Scholar Award / / Vallee Foundation /