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Title page for ETD etd-08102017-152412

Type of Document Dissertation
Author Willet, Alaina Hollister
Author's Email Address alaina.h.willet@vanderbilt.edu
URN etd-08102017-152412
Title Mechanisms Regulating Cytokinetic Contractile Ring Formation and Anchoring in Schizosaccharomyces pombe
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Irina Kaverina Committee Chair
Alissa Weaver Committee Member
Kathleen Gould Committee Member
Matthew Tyska Committee Member
Ryoma Ohi Committee Member
  • cytokinesis
  • fission yeast
Date of Defense 2017-07-19
Availability unrestricted
In Schizosaccharomyces pombe cytokinesis requires assembly and constriction of an actomyosin-based contractile ring (CR). Nucleation of F-actin for the CR requires a single essential formin, Cdc12, that localizes to the cell middle upon mitotic onset. The molecular mechanisms dictating its divison site targeting during cytokinesis are unknown. We defined that a Cdc12 N-terminal motif directly binds the F-BAR domain of the scaffolding protein Cdc15 and this interaction is controlled by Cdk1 phosphorylation of Cdc12. Phosphorylation of Cdc12 inhibits binding to the F-BAR Cdc15. cdc12 alleles that cannot bind Cdc15 or with all six Cdk1 sites mutated to phospho-mimetic residues show reduced Cdc12 cell division site accumulation and delayed CR formation. Thus Cdk1 phosphorylation of Cdc12 antagonizes its interaction with Cdc15 and its division site localization, consistent with a general role for Cdk1 in inhibiting cytokinesis until chromosome segregation is complete.

The CR is physically linked to the plasma membrane (PM). Cells lacking efr3, which encodes a conserved PM scaffold for the phosphatidylinositol 4-kinase Stt4, build CRs that can slide away from the cell middle in a myosin-V-dependent manner. The Efr3-dependent CR anchoring mechanism is distinct from previously reported pathways dependent on the F-BAR protein Cdc15 and paxillin. In efr3∆, the concentrations of several membrane-binding proteins were reduced in the CR and/or on the PM. Our results suggest that proper PM lipid composition is important to stabilize the central position of the CR and resist myosin V-based forces to promote the fidelity of cell division.

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