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FAM83D directs protein kinase CK1? to the mitotic spindle for proper spindle positioning

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 CK1?, 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? is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1?-binding-deficient FAM83DF283A/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? to the spindle in FAM83DF283A/F283A cells, rescues these defects. These findings implicate CK1? as new mitotic kinase that orchestrates the kinetics and orientation of cell division.

SUBMITTER: Mr. Luke, James Fulcher

PROVIDER: S-SCDT-EMBOR-2018-47495-T | biostudies-other |

REPOSITORIES: biostudies-other

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FAM83D directs protein kinase CK1? to the mitotic spindle for proper spindle positioning.

Project 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 CK1?, 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? is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1?-binding-deficient FAM83DF283A/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? to the spindle in FAM83DF283A/F283A cells, rescues these defects. These findings implicate CK1? as new mitotic kinase that orchestrates the kinetics and orientation of cell division.

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

Project 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 FAM83DF283A/F283A knockin mutation, 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 FAM83DF283A/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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Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle.

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Dynactin function in mitotic spindle positioning.

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