Mps1 phosphorylation sites regulate the function of centrin 2 in centriole assembly.

Ching-Hui Yang, Christopher Kasbek, Shubhra Majumder, Adlina Mohd Yusof, Harold A Fisk

Department of Molecular Genetics, Ohio State University, Columbus OH 43210-1292, USA.

Molecular biology of the cell 2010 Dec

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The nondegradable Mps1(Δ12/13) protein drives centriole overproduction, suggesting that Mps1 phosphorylates a subset of centrosomal proteins to drive the assembly of new centrioles. Here we identify three Mps1 phosphorylation sites within the centriolar protein Centrin 2 (Cetn2). Although centrioles can be assembled in the absence of Cetn2, centriole assembly is attenuated in the absence of Cetn2. While wild-type Cetn2 can compensate for this attenuation, a nonphosphorylatable version cannot. In addition, overexpressing Cetn2 causes Mps1-dependent centriole overproduction that requires each of the three Mps1 phosphorylation sites within Cetn2 and is greatly exacerbated by mimicking phosphorylation at any of these sites. Wild-type Cetn2 generates excess foci that are competent as mitotic spindle poles in HsSas-6-depleted cells, suggesting that Cetn2 can organize a subset of centriolar proteins independently of cartwheels. However, centriole overproduction caused by a phosphomimetic Cetn2 mutant requires HsSas-6, suggesting that Cetn2 phosphorylation stimulates the canonical centriole assembly pathway. Moreover, in the absence of Cetn2, Mps1(Δ12/13) cannot drive the production of mature centrioles capable of recruiting γ-Tubulin, and a nonphosphorylatable Cetn2 mutant cannot compensate for this defect and exacerbates Cetn2 depletion. Together, our data suggest that Mps1-dependent phosphorylation of Cetn2 stimulates the canonical centriole assembly pathway.

Citation

Ching-Hui Yang, Christopher Kasbek, Shubhra Majumder, Adlina Mohd Yusof, Harold A Fisk. Mps1 phosphorylation sites regulate the function of centrin 2 in centriole assembly. Molecular biology of the cell. 2010 Dec;21(24):4361-72