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

Willet AH, Bohnert KA, Gould KL
Mol Biol Cell. 2018 29 (6): 713-721

PMID: 29343550 · PMCID: PMC6003227 · DOI:10.1091/mbc.E17-11-0646

In , 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 hyperphosphorylated in M phase, we explored whether Cdc12 phosphoregulation 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, and phosphorylation on these sites inhibits its interaction with the Cdc15 F-BAR domain. Consistent with this finding, a mutant with all six Cdk1 sites changed to phosphomimetic residues () displays phenotypes similar to , 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.

© 2018 Willet et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (

MeSH Terms (11)

Actin Cytoskeleton Actins CDC2 Protein Kinase Cell Cycle Proteins Cell Division Cytokinesis Cytoskeletal Proteins GTP-Binding Proteins Phosphorylation Schizosaccharomyces Schizosaccharomyces pombe Proteins

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