Klebba and Galletta et al. reveal that the scaffold protein Asterless (Asl) regulates centriole duplication by controlling turnover of the kinase Plk4.

Cells must duplicate their centrioles once, and only once, per cell cycle. In interphase, the master regulator of centriole duplication, Plk4, triggers its own destruction by homodimerizing and phosphorylating itself. In mitosis, however, the phosphatase PP2A reverses this phosphorylation and stabilizes Plk4, allowing the kinase to accumulate on the surface of the mother centriole and license the assembly of a daughter centriole in the following S phase. Plk4 localizes to centrioles by binding to the N terminus of Asl. Surprisingly, given that low Plk4 levels are usually the limiting factor for centriole assembly, overexpressing Asl induces centriole overduplication, suggesting that the scaffold protein may have an additional function besides Plk4 recruitment.

Klebba and Galletta et al. found that overexpressing Asl’s C-terminal domain inhibited Plk4 turnover and induced centriole amplification in Drosophila S2 cells. This region of the protein contained a second binding site for Plk4, and mutating this site eliminated Asl’s ability to promote centriole duplication. Both the N- and C-terminal binding sites helped Asl form an oligomeric complex with Plk4 that stabilized the kinase during mitosis. In interphase cells, however, Asl’s N-terminal domain facilitated Plk4’s turnover by promoting the kinase’s dimerization and autophosphorylation.

The authors now want to investigate how Asl is regulated throughout the cell cycle and how the stable Asl–Plk4 complexes are organized on the surface of centrioles.

, et al
J. Cell Biol.

Author notes

Text by Ben Short