Fam83d Directs Protein Kinase Ck1 Alpha 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 cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1 alpha, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle positioning and timely cell division. CK1 alpha is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1 alpha-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 CK1 alpha to the spindle in FAM83D(F283A/F283A) cells, rescues these defects. These findings implicate CK1 alpha as new mitotic kinase that orchestrates the kinetics and orientation of cell division.