title: MICAL3 Flavoprotein Monooxygenase Forms a Complex with Centralspindlin and Regulates Cytokinesis.
abstract: During cytokinesis, the antiparallel array of microtubules forming the central spindle organizes the midbody, a structure that anchors the ingressed cleavage furrow and guides the assembly of abscission machinery. Here, we identified a role for the flavoprotein monooxygenase MICAL3, an actin disassembly factor, in organizing midbody-associated protein complexes. By combining cell biological assays with cross-linking mass spectrometry, we show that MICAL3 is recruited to the central spindle and the midbody through a direct interaction with the centralspindlin component MKLP1. Knock-out of MICAL3 leads to an increased frequency of cytokinetic failure and a delayed abscission. In a mechanism independent of its enzymatic activity, MICAL3 targets the adaptor protein ELKS and Rab8A-positive vesicles to the midbody, and the depletion of ELKS and Rab8A also leads to cytokinesis defects. We propose that MICAL3 acts as a midbody-associated scaffold for vesicle targeting, which promotes maturation of the intercellular bridge and abscission.
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: the Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Ka Lou
authors.initials: KL
authors.lastname: Yu
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Roderick
authors.initials: R
authors.lastname: Tas
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Sanne
authors.initials: S
authors.lastname: Remmelzwaal
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Serra-Marques
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.affiliation: the Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: From the Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht and a.akhmanova@uu.nl.
authors.forename: Anna
authors.identifier: 0000-0002-9048-8614
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C468925:ERC1 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C104434:spindlin; C561623:MICAL3 protein, human; D006899:Mixed Function Oxygenases; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins
keywords: actin; centralspindlin; cytokinesis; flavoprotein monooxygenase; mass spectrometry (MS); microtubule; midbody; protein cross-linking; vesicle transport