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WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin
WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further re...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240853/ https://www.ncbi.nlm.nih.gov/pubmed/34137789 http://dx.doi.org/10.1083/jcb.202007167 |
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author | Huang, Junjie Liang, Zhuobi Guan, Cuirong Hua, Shasha Jiang, Kai |
author_facet | Huang, Junjie Liang, Zhuobi Guan, Cuirong Hua, Shasha Jiang, Kai |
author_sort | Huang, Junjie |
collection | PubMed |
description | WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further reveal a TPX2–Aurora A–WDR62–katanin axis in cells. By combining cellular and in vitro experiments, we demonstrate that WDR62 shows preference for curved segments of dynamic GDP-MTs, as well as GMPCPP- and paclitaxel-stabilized MTs, suggesting that it recognizes extended MT lattice. Consistent with this property, WDR62 alone is inefficient in recruiting katanin to GDP-MTs, while WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. In addition, the MT-binding affinity of WDR62 is autoinhibited through JNK phosphorylation-induced intramolecular interaction. We propose that WDR62 is an atypical MAP and functions as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin to orchestrate the regulation of spindle dynamics. |
format | Online Article Text |
id | pubmed-8240853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82408532022-02-02 WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin Huang, Junjie Liang, Zhuobi Guan, Cuirong Hua, Shasha Jiang, Kai J Cell Biol Article WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further reveal a TPX2–Aurora A–WDR62–katanin axis in cells. By combining cellular and in vitro experiments, we demonstrate that WDR62 shows preference for curved segments of dynamic GDP-MTs, as well as GMPCPP- and paclitaxel-stabilized MTs, suggesting that it recognizes extended MT lattice. Consistent with this property, WDR62 alone is inefficient in recruiting katanin to GDP-MTs, while WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. In addition, the MT-binding affinity of WDR62 is autoinhibited through JNK phosphorylation-induced intramolecular interaction. We propose that WDR62 is an atypical MAP and functions as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin to orchestrate the regulation of spindle dynamics. Rockefeller University Press 2021-06-17 /pmc/articles/PMC8240853/ /pubmed/34137789 http://dx.doi.org/10.1083/jcb.202007167 Text en © 2021 Huang et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Huang, Junjie Liang, Zhuobi Guan, Cuirong Hua, Shasha Jiang, Kai WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin |
title | WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin |
title_full | WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin |
title_fullStr | WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin |
title_full_unstemmed | WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin |
title_short | WDR62 regulates spindle dynamics as an adaptor protein between TPX2/Aurora A and katanin |
title_sort | wdr62 regulates spindle dynamics as an adaptor protein between tpx2/aurora a and katanin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240853/ https://www.ncbi.nlm.nih.gov/pubmed/34137789 http://dx.doi.org/10.1083/jcb.202007167 |
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