title: The role of Cdc42 and Gic1 in the regulation of septin filament formation and dissociation.
abstract: Septins are guanine nucleotide-binding proteins that polymerize into filamentous and higher-order structures. Cdc42 and its effector Gic1 are involved in septin recruitment, ring formation and dissociation. The regulatory mechanisms behind these processes are not well understood. Here, we have used electron microscopy and cryo electron tomography to elucidate the structural basis of the Gic1-septin and Gic1-Cdc42-septin interaction. We show that Gic1 acts as a scaffolding protein for septin filaments forming long and flexible filament cables. Cdc42 in its GTP-form binds to Gic1, which ultimately leads to the dissociation of Gic1 from the filament cables. Surprisingly, Cdc42-GDP is not inactive, but in the absence of Gic1 directly interacts with septin filaments resulting in their disassembly. We suggest that this unanticipated dual function of Cdc42 is crucial for the cell cycle. Based on our results we propose a novel regulatory mechanism for septin filament formation and dissociation. DOI: http://dx.doi.org/10.7554/eLife.01085.001.
authors.affiliation: Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Yashar
authors.initials: Y
authors.lastname: Sadian
authors.forename: Christos
authors.initials: C
authors.lastname: Gatsogiannis
authors.forename: Csilla
authors.initials: C
authors.lastname: Patasi
authors.forename: Oliver
authors.initials: O
authors.lastname: Hofnagel
authors.forename: Roger S
authors.initials: RS
authors.lastname: Goody
authors.forename: Marian
authors.initials: M
authors.lastname: Farkasovský
authors.forename: Stefan
authors.initials: S
authors.lastname: Raunser
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D008854:Microscopy, Electron; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D058112:Septins / Q000096:biosynthesis* / Q000378:metabolism; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109252:GIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D058112:Septins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
keywords: Cdc42; Gic1; cell cycle; filaments; septin