McLamarrah, T.A., Buster, D.W., Galletta, B.J., Boese, C.J., Ryniawec, J.M., Hollingsworth, N.A., Byrnes, A.E., Brownlee, C.W., Slep, K.C., Rusan, N.M., Rogers, G.C. (2018). An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly.  J. Cell Biol. 217(4): 1217--1231.

FBrf0250617

Research paper

Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 is then phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STil/ANa2 (STAN) domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site. However, the physiological relevance of N-terminal phosphorylation was unknown. We found that Plk4 first phosphorylates the extreme N terminus of Ana2, which is critical for subsequent STAN domain modification. Phosphorylation of the central region then breaks the Plk4-Ana2 interaction. This phosphorylation pattern is important for centriole assembly and integrity because replacement of endogenous Ana2 with phospho-Ana2 mutants disrupts distinct steps in Ana2 function and inhibits centriole duplication.

PMC5881488 (PMC) (EuropePMC)