WDR62 and CEP170 recruit MAPKBP1 for pericentriolar material cohesion and mitotic spindle formation.

Abstract

Centrosomal and microtubule-associated proteins such as CEP170 and WDR62 are essential in regulating mitotic spindle formation and pole orientation during cell division. MAPKBP1, a paralog of WDR62, is also a centrosomal protein, but its function is currently unclear. We have shown here that MAPKBP1 is localised to the subdistal appendages of the mother centriole, the pericentriolar material (PCM) of the centrosomes and the mitotic spindles during metaphase. Furthermore, MAPKBP1, WDR62 and CEP170 exists as a complex, where MAPKBP1 is recruited to the centrosomes by WDR62 and CEP170, and CEP170-MAPKBP1 interaction is mediated by WDR62. In addition, MAPKBP1 depletion leads to mitotic spindle defects and delayed mitosis that were further exacerbated with WDR62 knockout, indicating a possible redundancy between MAPKBP1 and WDR62. MAPKBP1 loss also leads to PCM fragmentation, which supports its role as a subdistal appendages protein vital in maintaining centrosome structure and PCM cohesion for proper anchoring of mitotic spindles. This study provides insight into how subdistal appendages and centrosome and microtubule associated proteins co-operate to tightly regulate mitotic spindle formation and stability.