LAUSR

The Polo-like kinase homolog in Trypanosoma brucei, TbPLK, plays essential roles in basal body segregation, flagellum attachment and cytokinesis. The level of TbPLK protein is tightly controlled, but the underlying mechanism remains elusive. Here, we report a Cullin-RING ubiquitin ligase composed of Cullin4, the DNA damage-binding protein 1 homolog TbDDB1 and a WD40-repeat protein WDR1 that controls TbPLK abundance in the basal body and the bilobe. WDR1, through its C-terminal domain, interacts with the PEST motif in TbPLK and, through its N-terminal WD40 motif, binds to TbDDB1. Depletion of WDR1 inhibits bilobe duplication and basal body segregation, disrupts the assembly of the new flagellum attachment zone filament and detaches the new flagellum. Consistent with its role in TbPLK degradation, depletion of WDR1 causes excessive accumulation of TbPLK in the basal body and the bilobe, leading to continuous phosphorylation of TbCentrin2 in the bilobe at late cell cycle stages. Together, these results identify a novel WD40-repeat protein as a TbPLK receptor in the Cullin4-DDB1 ubiquitin ligase complex for degrading TbPLK in the basal body and the bilobe after the G1/S cell cycle transition, thereby promoting bilobe duplication, basal body separation and flagellum-cell body adhesion.