2. Academic Validation
  3. MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-containing Arp2/3 complexes

MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-containing Arp2/3 complexes

  • J Cell Biol. 2021 Aug 2;220(8):e202102043. doi: 10.1083/jcb.202102043.
Chiara Galloni # 1,  Davide Carra # 1,  Jasmine V G Abella 1,  Svend Kjær 2,  Pavithra Singaravelu 3 4,  David J Barry 5,  Naoko Kogata 1,  Christophe Guérin 3 4,  Laurent Blanchoin 3 4,  Michael Way 1 6
Affiliations

Affiliations

  • 1 Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, London, UK.
  • 2 Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.
  • 3 CytoMorpho Lab, Interdisciplinary Research Institute of Grenoble, Laboratoire de Physiologie Cellulaire & Végétale, University of Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Grenoble, France.
  • 4 CytoMorpho Lab, Institut de Recherche Saint Louis, University of Paris, Institut National de la Santé et de la Recherche Médicale, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Paris, France.
  • 5 Advanced Light Microscopy Facility, The Francis Crick Institute, London, UK.
  • 6 Department of Infectious Disease, Imperial College, London, UK.
  • # Contributed equally.
PMID: 34106209 DOI: 10.1083/jcb.202102043
Abstract

The mechanisms regulating the disassembly of branched actin networks formed by the Arp2/3 complex still remain to be fully elucidated. In addition, the impact of Arp3 isoforms on the properties of Arp2/3 are also unexplored. We now demonstrate that Arp3 and Arp3B isocomplexes promote actin assembly equally efficiently but generate branched actin networks with different disassembly rates. Arp3B dissociates significantly faster than Arp3 from the network, and its depletion increases actin stability. This difference is due to the oxidation of Arp3B, but not Arp3, by the methionine monooxygenase MICAL2, which is recruited to the actin network by coronin 1C. Substitution of Arp3B Met293 by threonine, the corresponding residue in Arp3, increases actin network stability. Conversely, replacing Arp3 Thr293 with glutamine to mimic Met oxidation promotes disassembly. The ability of MICAL2 to enhance network disassembly also depends on cortactin. Our observations demonstrate that coronin 1C, cortactin, and MICAL2 act together to promote disassembly of branched actin networks by oxidizing Arp3B-containing Arp2/3 complexes.

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