Cargando…

FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning

The concerted action of many protein kinases helps orchestrate the error‐free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin‐dependent kinases, are well established. However, these and other known mitotic kinases alone canno...

Descripción completa

Detalles Bibliográficos
Autores principales: Fulcher, Luke J, He, Zhengcheng, Mei, Lin, Macartney, Thomas J, Wood, Nicola T, Prescott, Alan R, Whigham, Arlene J, Varghese, Joby, Gourlay, Robert, Ball, Graeme, Clarke, Rosemary, Campbell, David G, Maxwell, Christopher A, Sapkota, Gopal P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726907/
https://www.ncbi.nlm.nih.gov/pubmed/31338967
http://dx.doi.org/10.15252/embr.201847495
_version_ 1783449173642706944
author Fulcher, Luke J
He, Zhengcheng
Mei, Lin
Macartney, Thomas J
Wood, Nicola T
Prescott, Alan R
Whigham, Arlene J
Varghese, Joby
Gourlay, Robert
Ball, Graeme
Clarke, Rosemary
Campbell, David G
Maxwell, Christopher A
Sapkota, Gopal P
author_facet Fulcher, Luke J
He, Zhengcheng
Mei, Lin
Macartney, Thomas J
Wood, Nicola T
Prescott, Alan R
Whigham, Arlene J
Varghese, Joby
Gourlay, Robert
Ball, Graeme
Clarke, Rosemary
Campbell, David G
Maxwell, Christopher A
Sapkota, Gopal P
author_sort Fulcher, Luke J
collection PubMed
description The concerted action of many protein kinases helps orchestrate the error‐free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin‐dependent kinases, are well established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1α, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle positioning and timely cell division. CK1α is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1α‐binding‐deficient FAM83D (F283A/F283A) knockin mutations, display pronounced spindle positioning defects, and a prolonged mitosis. Restoring FAM83D at the endogenous locus in FAM83D (−/−) cells, or artificially delivering CK1α to the spindle in FAM83D (F283A/F283A) cells, rescues these defects. These findings implicate CK1α as new mitotic kinase that orchestrates the kinetics and orientation of cell division.
format Online
Article
Text
id pubmed-6726907
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-67269072019-09-10 FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning Fulcher, Luke J He, Zhengcheng Mei, Lin Macartney, Thomas J Wood, Nicola T Prescott, Alan R Whigham, Arlene J Varghese, Joby Gourlay, Robert Ball, Graeme Clarke, Rosemary Campbell, David G Maxwell, Christopher A Sapkota, Gopal P EMBO Rep Articles The concerted action of many protein kinases helps orchestrate the error‐free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin‐dependent kinases, are well established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1α, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle positioning and timely cell division. CK1α is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1α‐binding‐deficient FAM83D (F283A/F283A) knockin mutations, display pronounced spindle positioning defects, and a prolonged mitosis. Restoring FAM83D at the endogenous locus in FAM83D (−/−) cells, or artificially delivering CK1α to the spindle in FAM83D (F283A/F283A) cells, rescues these defects. These findings implicate CK1α as new mitotic kinase that orchestrates the kinetics and orientation of cell division. John Wiley and Sons Inc. 2019-07-24 2019-09 /pmc/articles/PMC6726907/ /pubmed/31338967 http://dx.doi.org/10.15252/embr.201847495 Text en © 2019 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Fulcher, Luke J
He, Zhengcheng
Mei, Lin
Macartney, Thomas J
Wood, Nicola T
Prescott, Alan R
Whigham, Arlene J
Varghese, Joby
Gourlay, Robert
Ball, Graeme
Clarke, Rosemary
Campbell, David G
Maxwell, Christopher A
Sapkota, Gopal P
FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
title FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
title_full FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
title_fullStr FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
title_full_unstemmed FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
title_short FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning
title_sort fam83d directs protein kinase ck1α to the mitotic spindle for proper spindle positioning
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726907/
https://www.ncbi.nlm.nih.gov/pubmed/31338967
http://dx.doi.org/10.15252/embr.201847495
work_keys_str_mv AT fulcherlukej fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT hezhengcheng fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT meilin fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT macartneythomasj fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT woodnicolat fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT prescottalanr fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT whighamarlenej fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT varghesejoby fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT gourlayrobert fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT ballgraeme fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT clarkerosemary fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT campbelldavidg fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT maxwellchristophera fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning
AT sapkotagopalp fam83ddirectsproteinkinaseck1atothemitoticspindleforproperspindlepositioning