TY - JOUR
T1 - Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes
AU - Stahley, Sara N.
AU - Basta, Lena P.
AU - Sharan, Rishabh
AU - Devenport, Danelle
N1 - Funding Information:
The authors are grateful to all those who provided resources, technical support, and helpful suggestions that influenced this work. We thank members of the Devenport laboratory for their advice and insightful discussions, especially Katherine Little for reagent generation and manuscript editing, and Dr. Maureen Cetera for critical feedback during manuscript preparation. We thank Gary Laevsky in the Princeton University Confocal Imaging Facility, a Nikon Center of Excellence, for imaging assistance and expertise. We also thank Christina DeCoste and Katherine Rittenbach in the Princeton University Flow Cytometry Resource Facility for assistance with cell sorting. We appreciate those in Princeton University’s Laboratory Animal Resources. We kindly thank Dr Elaine Fuchs for the generous donation of the Celsr1Crsh/+ mouse line and the Rutgers Cancer Institute of New Jersey Genome Editing Shared Resource for rederivation services with funding, in part, from the National Cancer Institute of the National Institutes of Health. This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Vallee Foundation.
Funding Information:
The authors are grateful to all those who provided resources, technical support, and helpful suggestions that influenced this work. We thank members of the Devenport laboratory for their advice and insightful discussions, especially Katherine Little for reagent generation and manuscript editing, and Dr. Maureen Cetera for critical feedback during manuscript preparation. We thank Gary Laevsky in the Princeton University Confocal Imaging Facility, a Nikon Center of Excellence, for imaging assistance and expertise. We also thank Christina DeCoste and Katherine Rittenbach in the Princeton University Flow Cytometry Resource Facility for assistance with cell sorting. We appreciate those in Princeton University?s Laboratory Animal Resources. We kindly thank Dr Elaine Fuchs for the gener-ous donation of the Celsr1Crsh/+ mouse line and the Rutgers Cancer Institute of New Jersey Genome Editing Shared Resource for rederivation services with funding, in part, from the National Cancer Institute of the National Institutes of Health. This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Vallee Foundation.
Publisher Copyright:
© Stahley et al.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.62097
DO - 10.7554/eLife.62097
M3 - Article
C2 - 33529151
AN - SCOPUS:85100752552
SN - 2050-084X
VL - 10
SP - 1
EP - 26
JO - eLife
JF - eLife
M1 - e62097
ER -