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
Volume20
Issue number9
Early online date24 Jul 2019
DOIs
Publication statusPublished - 1 Sep 2019

Keywords

  • CK1
  • FAM83D
  • kinase
  • mitosis
  • spindle positioning

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    Fulcher, L. J., He, Z., Mei, L., Macartney, T. J., Wood, N. T., Prescott, A. R., Whigham, A., Varghese, J., Gourlay, R., Ball, G., Clarke, R., Campbell, D., Maxwell, C. A., & Sapkota, G. P. (2019). FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning. EMBO Reports, 20(9), 1-19. [e47495]. https://doi.org/10.15252/embr.201847495