Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes. Author Sara Stahley, Lena Basta, Rishabh Sharan, Danelle Devenport Publication Year 2021 Type Journal Article 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 - and -interactions, and organizes into dense and highly stable punctate assemblies. We provide evidence suggesting that PCP-mutant variant of Celsr1, Celsr1, selectively impairs lateral -interactions. Although Celsr1 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 -dimerization. Using biochemical and super-resolution microscopy approaches, we show that although Celsr1 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 -adhesive homodimeric bridge, but also as an organizer of intercellular Frizzled6 and Vangl2 asymmetry through lateral, -interactions. Keywords Animals, Mice, Humans, Cell Line, Female, Male, Embryo, Mammalian, Cell Polarity, Keratinocytes, Receptors, G-Protein-Coupled, Frizzled Receptors Journal Elife Volume 10 Date Published 2021 Feb 02 ISSN Number 2050-084X DOI 10.7554/eLife.62097 Alternate Journal Elife PMCID PMC7857726 PMID 33529151 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML