Oxidation of F-actin controls the terminal steps of cytokinesis

Nat Commun. 2017 Feb 23;8:14528. doi: 10.1038/ncomms14528.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cytokinesis*
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Guanosine Triphosphate / metabolism
  • HeLa Cells
  • Humans
  • LIM Domain Proteins / chemistry
  • LIM Domain Proteins / metabolism
  • Microfilament Proteins
  • Mixed Function Oxygenases
  • Models, Biological
  • Oxidation-Reduction
  • Polymerization
  • Protein Binding
  • Protein Domains
  • Protein Structure, Secondary
  • Protein Transport
  • rab GTP-Binding Proteins / metabolism

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • CHMP4B protein, human
  • Cytoskeletal Proteins
  • Endosomal Sorting Complexes Required for Transport
  • LIM Domain Proteins
  • Microfilament Proteins
  • Guanosine Triphosphate
  • MICAL1 protein, human
  • Mixed Function Oxygenases
  • RAB35 protein, human
  • rab GTP-Binding Proteins