Journal Article

Oxidation of F-actin controls the terminal steps of cytokinesis

Pylypenko, Olena, Wioland, Hugo, Frémont, Stéphane, Hammich, Hussein, Rocancourt, Murielle, Echard, Arnaud, Houdusse, Anne, Romet-Lemonne, Guillaume, Bai, Jian, Klinkert, Kerstin, Stroebel, David, Kikuti, Carlos

2017

Overview

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. Cytokinetic abscission relies on the local constriction after cytoskeleton disassembly, but it is not known how the actin filaments are disassembled. Here, the authors show that the redox enzyme MICAL1 is recruited by Rab35 and induces oxidation-mediated depolymerization of actin, which is required to recruit ESCRT-III and complete abscission.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/19 / 631/80/128/1276 / 631/80/641/2090 / Abscission / Actin Cytoskeleton - metabolism / Actins - metabolism / Adaptor Proteins, Signal Transducing - chemistry / Adaptor Proteins, Signal Transducing - metabolism / Cell division / Cytokinesis / Cytoskeletal Proteins - chemistry / Cytoskeletal Proteins - metabolism / Cytoskeleton / Endosomal Sorting Complexes Required for Transport - metabolism / Enzymes / Guanosine Triphosphate - metabolism / HeLa Cells / Humanities and Social Sciences / Humans / Insects / Life Sciences / LIM Domain Proteins - chemistry / LIM Domain Proteins - metabolism / Models, Biological / multidisciplinary / Oxidation / Oxidation-Reduction / Polymerization / Protein Binding / Protein Domains / Protein Structure, Secondary / Protein Transport / rab GTP-Binding Proteins - metabolism / Roles / Science / Science (multidisciplinary)