title: Oxidation of F-actin controls the terminal steps of cytokinesis.
abstract: Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission. MICAL1 is recruited to the abscission site by the Rab35 GTPase through a direct interaction with a flat three-helix domain found in MICAL1 C terminus. Mechanistically, in vitro assays on single actin filaments demonstrate that MICAL1 is activated by Rab35. Moreover, in our experimental conditions, MICAL1 does not act as a severing enzyme, as initially thought, but instead induces F-actin depolymerization from both ends. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division.
authors.affiliation: Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France.|Centre National de la Recherche Scientifique UMR3691, 75015 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Frémont
authors.affiliation: Structural Motility, Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: Hammich
authors.affiliation: Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France.|Centre National de la Recherche Scientifique UMR3691, 75015 Paris, France.|Sorbonne Universités, UPMC Univ Paris06, Sorbonne Universités, IFD, 4 Place Jussieu, 75252 Paris Cedex 15, France.
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.affiliation: Institut Jacques Monod, CNRS, Université Paris Diderot, Université Sorbonne Paris Cité, 75013 Paris, France.
authors.forename: Hugo
authors.identifier: 0000-0001-5254-9642
authors.initials: H
authors.lastname: Wioland
authors.affiliation: Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France.|Centre National de la Recherche Scientifique UMR3691, 75015 Paris, France.|Sorbonne Universités, UPMC Univ Paris06, Sorbonne Universités, IFD, 4 Place Jussieu, 75252 Paris Cedex 15, France.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Klinkert
authors.affiliation: Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France.|Centre National de la Recherche Scientifique UMR3691, 75015 Paris, France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Rocancourt
authors.affiliation: Structural Motility, Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Kikuti
authors.affiliation: Ecole Normale Supérieure, PSL Research University, CNRS, INSERM, Institut de Biologie de l'École Normale Supérieure (IBENS), 75005 Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Stroebel
authors.affiliation: Institut Jacques Monod, CNRS, Université Paris Diderot, Université Sorbonne Paris Cité, 75013 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Romet-Lemonne
authors.affiliation: Structural Motility, Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Olena
authors.initials: O
authors.lastname: Pylypenko
authors.affiliation: Structural Motility, Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Houdusse
authors.affiliation: Membrane Traffic and Cell Division Lab, Cell Biology and Infection Department Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France.|Centre National de la Recherche Scientifique UMR3691, 75015 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Echard
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D048749:Cytokinesis; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000737:chemistry / Q000378:metabolism; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D008954:Models, Biological; D010084:Oxidation-Reduction; D058105:Polymerization; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000096985:Calponins
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D006160:Guanosine Triphosphate; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D020691:rab GTP-Binding Proteins; C478397:CHMP4B protein, human; C455272:MICAL1 protein, human; D000096985:Calponins; C511183:RAB35 protein, human