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Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions

The adherens junction (AJ) plays a crucial role in maintaining cell–cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end–directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule mi...

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Autores principales: Sako-Kubota, Kyoko, Tanaka, Nobutoshi, Nagae, Shigenori, Meng, Wenxiang, Takeichi, Masatoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244195/
https://www.ncbi.nlm.nih.gov/pubmed/25253721
http://dx.doi.org/10.1091/mbc.E14-07-1245
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author Sako-Kubota, Kyoko
Tanaka, Nobutoshi
Nagae, Shigenori
Meng, Wenxiang
Takeichi, Masatoshi
author_facet Sako-Kubota, Kyoko
Tanaka, Nobutoshi
Nagae, Shigenori
Meng, Wenxiang
Takeichi, Masatoshi
author_sort Sako-Kubota, Kyoko
collection PubMed
description The adherens junction (AJ) plays a crucial role in maintaining cell–cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end–directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule minus ends. The function of junction-associated KIFC3, however, remains to be elucidated. Here we find that KIFC3 binds the ubiquitin-specific protease USP47, a protease that removes ubiquitin chains from substrates and hence inhibits proteasome-mediated proteolysis, and recruits it to AJs. Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region of the cytoplasmic domain, resulting in the production of a 90-kDa fragment and the internalization of E-cadherin. This cleavage depends on the E3 ubiquitin protein ligase Hakai and is inhibited by proteasome inhibitors. E-cadherin ubiquitination consistently increases after depletion of KIFC3 or USP47. These findings suggest that KIFC3 suppresses the ubiquitination and resultant degradation of E-cadherin by recruiting USP47 to AJs, a process that may be involved in maintaining stable cell–cell adhesion in epithelial sheets.
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spelling pubmed-42441952015-02-16 Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions Sako-Kubota, Kyoko Tanaka, Nobutoshi Nagae, Shigenori Meng, Wenxiang Takeichi, Masatoshi Mol Biol Cell Articles The adherens junction (AJ) plays a crucial role in maintaining cell–cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end–directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule minus ends. The function of junction-associated KIFC3, however, remains to be elucidated. Here we find that KIFC3 binds the ubiquitin-specific protease USP47, a protease that removes ubiquitin chains from substrates and hence inhibits proteasome-mediated proteolysis, and recruits it to AJs. Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region of the cytoplasmic domain, resulting in the production of a 90-kDa fragment and the internalization of E-cadherin. This cleavage depends on the E3 ubiquitin protein ligase Hakai and is inhibited by proteasome inhibitors. E-cadherin ubiquitination consistently increases after depletion of KIFC3 or USP47. These findings suggest that KIFC3 suppresses the ubiquitination and resultant degradation of E-cadherin by recruiting USP47 to AJs, a process that may be involved in maintaining stable cell–cell adhesion in epithelial sheets. The American Society for Cell Biology 2014-12-01 /pmc/articles/PMC4244195/ /pubmed/25253721 http://dx.doi.org/10.1091/mbc.E14-07-1245 Text en © 2014 Sako-Kubota et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Sako-Kubota, Kyoko
Tanaka, Nobutoshi
Nagae, Shigenori
Meng, Wenxiang
Takeichi, Masatoshi
Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
title Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
title_full Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
title_fullStr Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
title_full_unstemmed Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
title_short Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
title_sort minus end–directed motor kifc3 suppresses e-cadherin degradation by recruiting usp47 to adherens junctions
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244195/
https://www.ncbi.nlm.nih.gov/pubmed/25253721
http://dx.doi.org/10.1091/mbc.E14-07-1245
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