FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning. (24th July 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EMBO reports. Volume 20:Number 9(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-07-24
• Subjects: CK1 -- FAM83D -- kinase -- mitosis -- spindle positioning; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201847495
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: FAM83D delivers the serine/threonine protein kinase CK1α to the mitotic spindle to ensure correct spindle positioning and smooth progression through mitosis. FAM83D interacts and co‐localises with CK1α at the centrosome and spindle during mitosis. Disruption of FAM83D‐CK1α interaction prevents CK1α recruitment to the spindle. FAMD83‐CK1α interaction is required for proper spindle positioning and timely metaphase‐to‐anaphase transition. Abstract : FAM83D delivers the serine/threonine protein kinase CK1α to the mitotic spindle to ensure correct spindle positioning and smooth progression through mitosis.