3 years ago

Cdk1-dependent phospho-inhibition of a formin-F-BAR interaction opposes cytokinetic contractile ring formation.

Alaina H Willet, Kathleen L Gould, K Adam Bohnert
In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12, localizes to the cell middle upon mitotic onset and nucleates the F-actin of the CR. Cdc12 medial recruitment is mediated in part by its direct binding to the F-BAR scaffold Cdc15. Given that Cdc12 is hyper-phosphorylated in M phase, we explored whether Cdc12 phospho-regulation impacts its association with Cdc15 during mitosis. We found that Cdk1, a major mitotic kinase, phosphorylates Cdc12 on six N-terminal residues near the Cdc15-binding site. Cdc12 phosphorylation of Cdc12 on these sites inhibits its interaction with the Cdc15 F-BAR domain. Consistent with this finding, a cdc12 mutant with all six Cdk1 sites changed to phospho-mimetic residues (cdc12-6D) displays similar phenotypes to cdc12-P31A, in which the Cdc15-binding motif is disrupted; both show reduced Cdc12 at the CR and delayed CR formation. Together, these results indicate that Cdk1 phosphorylation of formin Cdc12 antagonizes its interaction with Cdc15 and thereby opposes Cdc12's CR localization. These results are consistent with a general role for Cdk1 in inhibiting cytokinesis until chromosome segregation is complete.

Publisher URL: http://doi.org/10.1091/mbc.E17-11-0646

DOI: 10.1091/mbc.E17-11-0646

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