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Calcium-dependent dynamics of cadherin interactions at cell–cell junctions

Kim, Sally A. and Tai, Chin-Yin and Mok, Lee-Peng and Mosser, Eric A. and Schuman, Erin M. (2011) Calcium-dependent dynamics of cadherin interactions at cell–cell junctions. Proceedings of the National Academy of Sciences of the United States of America, 108 (24). pp. 9857-9862. ISSN 0027-8424. https://resolver.caltech.edu/CaltechAUTHORS:20110624-094705879

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Abstract

Cadherins play a key role in the dynamics of cell–cell contact formation and remodeling of junctions and tissues. Cadherin–cadherin interactions are gated by extracellular Ca^(2+), which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (τ = 1.17 ± 0.06 s^(−1)) upon chelation of extracellular Ca^(2+). A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (τ = 0.86 ± 0.02 s^(−1)), suggesting two types of native cadherin interactions—one that is rapidly modulated by changes in extracellular Ca^(2+) and another with relatively stable adhesive activity that is Ca^(2+) independent. The Ca^(2+)-sensitive dynamics of cadherin interactions were transmitted to the cell interior where β-catenin translocated to N-cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1019003108 DOIUNSPECIFIED
http://www.pnas.org/content/108/24/9857PublisherUNSPECIFIED
Additional Information:© 2011 National Academy of Sciences. Edited by Barry H. Honig, Columbia University/Howard Hughes Medical Institute, New York, NY, and approved May 2, 2011 (received for review December 17, 2010). Published online before print May 25, 2011. We thank Anh Pham for assistance and the Benson and Piston laboratories for providing the pCXN2-Ncad and mCerulean constructs. We also thank members of the Schuman laboratory, particularly Hwan-Ching Tai and Young Yoon, for helpful discussions, and David Sprinzak, Michael Sutton, Stephanie Bunse, Kaushiki Menon, and especially Kai Zinn, for critical comments on the manuscript. This work was funded by the National Institutes of Health and the Howard Hughes Medical Institute (E.M.S.). S.A.K. was a Damon Runyon Fellow supported by Damon Runyon Cancer Research Foundation Grant DRG-1908-06. Author contributions: S.A.K., C.-Y.T., L.-P.M., E.A.M., and E.M.S. designed research; S.A.K., C.-Y.T., and L.-P.M. performed research; S.A.K., C.-Y.T., and L.-P.M. contributed new reagents/analytic tools; S.A.K., C.Y.T., and L.-P.M. analyzed data; and S.A.K. and E.M.S. wrote the paper.
Funders:
Funding AgencyGrant Number
NIHUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Damon Runyon Cancer Research FoundationDRG-1908-06
Subject Keywords:cell adhesion; fluorescence resonance energy transfer; trans binding
Issue or Number:24
Record Number:CaltechAUTHORS:20110624-094705879
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110624-094705879
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24195
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:24 Jun 2011 20:07
Last Modified:03 Oct 2019 02:54

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