title: Dephosphorylation of F-BAR protein Cdc15 modulates its conformation and stimulates its scaffolding activity at the cell division site.
abstract: Cytokinesis in Schizosaccharomyces pombe requires the function of Cdc15, the founding member of the pombe cdc15 homology (PCH) family of proteins. As an early, abundant contractile ring component with multiple binding partners, Cdc15 plays a key role in organizing the ring. We demonstrate that Cdc15 phosphorylation at many sites generates a closed conformation, inhibits Cdc15 assembly at the division site in interphase, and precludes interaction of Cdc15 with its binding partners. Cdc15 dephosphorylation induces an open conformation, oligomerization, and scaffolding activity during mitosis. Cdc15 mutants with reduced phosphorylation precociously appear at the division site in filament-like structures and display increased association with protein partners and the membrane. Our results indicate that Cdc15 phosphoregulation impels both assembly and disassembly of the contractile apparatus and suggest a regulatory strategy that PCH family and BAR superfamily members might broadly employ to achieve temporal specificity in their roles as linkers between membrane and cytoskeleton.
authors.affiliation: Howard Hughes Medical Institute and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Roberts-Galbraith
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Ohi
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.forename: Jun-Song
authors.initials: JS
authors.lastname: Chen
authors.forename: Ian
authors.initials: I
authors.lastname: McLeod
authors.forename: W Hayes
authors.initials: WH
authors.lastname: McDonald
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gould
mesh_terms: D000409:Alanine / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C082279:CDC15 protein; C531994:Cdc12 protein, S pombe; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D050505:Mutant Proteins; D029702:Schizosaccharomyces pombe Proteins; D019204:GTP-Binding Proteins; D000409:Alanine