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

Luke J. Fulcher, Zhengcheng He, Lin Mei, Thomas J. Macartney, Nicola T. Wood, Alan R. Prescott, Arlene Whigham, Joby Varghese, Robert Gourlay, Graeme Ball, Rosemary Clarke, David Campbell, Christopher A. Maxwell, Gopal P. Sapkota (Lead / Corresponding author)

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Abstract

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.

Original languageEnglish
Article numbere47495
Pages (from-to)1-19
Number of pages19
JournalEMBO Reports
DOIs
Publication statusPublished - 24 Jul 2019

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Casein Kinase I
Spindle Apparatus
Phosphotransferases
Cells
Mitosis
Protein Kinases
Cell Division
Defects
Phosphorylation
Cyclin-Dependent Kinases
Display devices
Kinetics
Mutation
Proteins

Keywords

  • CK1
  • FAM83D
  • kinase
  • mitosis
  • spindle positioning

Cite this

Fulcher, Luke J. ; He, Zhengcheng ; Mei, Lin ; Macartney, Thomas J. ; Wood, Nicola T. ; Prescott, Alan R. ; Whigham, Arlene ; Varghese, Joby ; Gourlay, Robert ; Ball, Graeme ; Clarke, Rosemary ; Campbell, David ; Maxwell, Christopher A. ; Sapkota, Gopal P. / FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning. In: EMBO Reports. 2019 ; pp. 1-19.
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abstract = "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.",
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note = "Funding: LJF is supported by the U.K. MRC PhD studentship. The Dundee Imaging Facility is funded by the “MRC Next Generation Optical Microscopy” award [MR/K015869/1]. LJF also receives funding from the Queens College Scholarship, University of Dundee. CAM is supported by the Michael Cuccione Foundation and the Canadian Institutes of Health Research (New Investigator Salary Award and Operating Grant OBC_134038). GPS is supported by the U.K. MRC (Grant MC_UU_12016/3) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy (Boehringer-Ingelheim, GlaxoSmithKline, Merck-Serono).",
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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; Varghese, Joby; Gourlay, Robert; Ball, Graeme; Clarke, Rosemary; Campbell, David; Maxwell, Christopher A.; Sapkota, Gopal P. (Lead / Corresponding author).

In: EMBO Reports, 24.07.2019, p. 1-19.

Research output: Contribution to journalArticle

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AU - Fulcher, Luke J.

AU - He, Zhengcheng

AU - Mei, Lin

AU - Macartney, Thomas J.

AU - Wood, Nicola T.

AU - Prescott, Alan R.

AU - Whigham, Arlene

AU - Varghese, Joby

AU - Gourlay, Robert

AU - Ball, Graeme

AU - Clarke, Rosemary

AU - Campbell, David

AU - Maxwell, Christopher A.

AU - Sapkota, Gopal P.

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PY - 2019/7/24

Y1 - 2019/7/24

N2 - 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.

AB - 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.

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