Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782346207510659072 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4244195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sakokubotakyoko minusenddirectedmotorkifc3suppressesecadherindegradationbyrecruitingusp47toadherensjunctions AT tanakanobutoshi minusenddirectedmotorkifc3suppressesecadherindegradationbyrecruitingusp47toadherensjunctions AT nagaeshigenori minusenddirectedmotorkifc3suppressesecadherindegradationbyrecruitingusp47toadherensjunctions AT mengwenxiang minusenddirectedmotorkifc3suppressesecadherindegradationbyrecruitingusp47toadherensjunctions AT takeichimasatoshi minusenddirectedmotorkifc3suppressesecadherindegradationbyrecruitingusp47toadherensjunctions |