dc.creator | Willet, Alaina Hollister | |
dc.date.accessioned | 2020-08-22T20:45:45Z | |
dc.date.available | 2018-02-07 | |
dc.date.issued | 2017-08-11 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08102017-152412 | |
dc.identifier.uri | http://hdl.handle.net/1803/13870 | |
dc.description.abstract | 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. | |
dc.format.mimetype | application/pdf | |
dc.subject | cytokinesis | |
dc.subject | fission yeast | |
dc.title | Mechanisms Regulating Cytokinetic
Contractile Ring Formation and
Anchoring in Schizosaccharomyces
pombe | |
dc.type | dissertation | |
dc.contributor.committeeMember | Kathleen Gould | |
dc.contributor.committeeMember | Matthew Tyska | |
dc.contributor.committeeMember | Ryoma Ohi | |
dc.contributor.committeeMember | Alissa Weaver | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2018-02-07 | |
local.embargo.lift | 2018-02-07 | |
dc.contributor.committeeChair | Irina Kaverina | |