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Campbell, D. G.

Publications and source records attributed to Campbell, D. G..

2 recordsLinked to original sources

FAM83D directs protein kinase CK1α 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, 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 mutation, 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.

cell biology↗

FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Our previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.\n\nSummary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.

cell biology↗