title: SIN-dependent phosphoinhibition of formin multimerization controls fission yeast cytokinesis.
abstract: Many eukaryotes accomplish cell division by building and constricting a medial actomyosin-based cytokinetic ring (CR). In Schizosaccharomyces pombe, a Hippo-related signaling pathway termed the septation initiation network (SIN) controls CR formation, maintenance, and constriction. However, how the SIN regulates integral CR components was unknown. Here, we identify the essential cytokinetic formin Cdc12 as a key CR substrate of SIN kinase Sid2. Eliminating Sid2-mediated Cdc12 phosphorylation leads to persistent Cdc12 clustering, which prevents CR assembly in the absence of anillin-like Mid1 and causes CRs to collapse when cytokinesis is delayed. Molecularly, Sid2 phosphorylation of Cdc12 abrogates multimerization of a previously unrecognized Cdc12 domain that confers F-actin bundling activity. Taken together, our findings identify a SIN-triggered oligomeric switch that modulates cytokinetic formin function, revealing a novel mechanism of actin cytoskeleton regulation during cell division.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA;
authors.forename: K Adam
authors.initials: KA
authors.lastname: Bohnert
authors.forename: Agnieszka P
authors.initials: AP
authors.lastname: Grzegorzewska
authors.forename: Alaina H
authors.initials: AH
authors.lastname: Willet
authors.forename: Craig W
authors.initials: CW
authors.lastname: Vander Kooi
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gould
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: C531994:Cdc12 protein, S pombe; D003598:Cytoskeletal Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C113816:Sid2 protein, S pombe
keywords: F-actin bundling; cytokinesis; formin; oligomerization; phosphorylation; septation initiation network