Actin reduction by MsrB2 is a key component of the cytokinetic abscission checkpoint and prevents tetraploidy
| Autor: | Arnaud Echard, Hugo Wioland, Frédérique Cuvelier, Guillaume Romet-Lemonne, Tamara Advedissian, Jian Bai |
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| Přispěvatelé: | Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Work in the A.E. laboratory has been supported by Institut Pasteur, CNRS, and the Agence Nationale de la Recherche (ANR) (AbsCystem and RedoxActin). J.B. was supported by the Pasteur-Paris University (PPU) international PhD program and received a fellowship from Fondation ARC pour la Recherche sur le Cancer (DOC20180507410). H.W. has been supported by a postdoctoral fellowship from the Fondation ARC pour la Recherche sur le Cancer. T.A. has been supported by a postdoctoral fellowship from the Fondation pour la Recherche Médicale (FRM SPF201809006907) and the ANR (Cytosign)., ANR-15-CE13-0001,AbsCyStem,Régulation de l'abscission dans les cellules animales(2015), ANR-19-CE13-0018,RedoxActin,Régulation du cytosquelette d'actine par le contrôle de son oxydation(2019), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP) |
| Rok vydání: | 2020 |
| Předmět: |
MESH: Oxidation-Reduction
Cell division MESH: Drosophila Mixed Function Oxygenases MESH: Endosomal Sorting Complexes Required for Transport Drosophila Proteins MESH: Animals Cytoskeleton 0303 health sciences Multidisciplinary Chemistry Microfilament Proteins 030302 biochemistry & molecular biology cytoskeleton Biological Sciences MESH: Mixed Function Oxygenases Chromatin Cell biology MESH: Methionine Sulfoxide Reductases Midbody Drosophila Oxidation-Reduction actin MESH: Cytokinesis MESH: Drosophila Proteins Aurora B kinase Mitosis cytokinesis [SDV.BC]Life Sciences [q-bio]/Cellular Biology macromolecular substances MESH: Actins Cell Line MESH: Chromatin MESH: Microfilament Proteins 03 medical and health sciences Abscission Animals Humans Actin 030304 developmental biology MESH: Humans Endosomal Sorting Complexes Required for Transport MESH: Mitosis abscission checkpoint Actins MESH: Cell Line oxidoreduction Methionine Sulfoxide Reductases MESH: HeLa Cells Cytokinesis HeLa Cells |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2020, 117 (8), pp.4169-4179. ⟨10.1073/pnas.1911629117⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2020, 117 (8), pp.4169-4179. ⟨10.1073/pnas.1911629117⟩ Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1911629117 |
| Popis: | International audience; Abscission is the terminal step of cytokinesis leading to the physical separation of the daughter cells. In response to the abnormal presence of lagging chromatin between dividing cells, an evolutionarily conserved abscission/NoCut checkpoint delays abscission and prevents formation of binucleated cells by stabilizing the cytokinetic intercellular bridge (ICB). How this bridge is stably maintained for hours while the checkpoint is activated is poorly understood and has been proposed to rely on F-actin in the bridge region. Here, we show that actin polymerization is indeed essential for stabilizing the ICB when lagging chromatin is present, but not in normal dividing cells. Mechanistically, we found that a cytosolic pool of human methionine sulfoxide reductase B2 (MsrB2) is strongly recruited at the midbody in response to the presence of lagging chromatin and functions within the ICB to promote actin polymerization there. Consistently, in MsrB2-depleted cells, F-actin levels are decreased in ICBs, and dividing cells with lagging chromatin become binucleated as a consequence of unstable bridges. We further demonstrate that MsrB2 selectively reduces oxidized actin monomers and thereby counteracts MICAL1, an enzyme known to depolymerize actin filaments by direct oxidation. Finally, MsrB2 colocalizes and genetically interacts with the checkpoint components Aurora B and ANCHR, and the abscission delay upon checkpoint activation by nuclear pore defects also depends on MsrB2. Altogether, this work reveals that actin reduction by MsrB2 is a key component of the abscission checkpoint that favors F-actin polymerization and limits tetraploidy, a starting point for tumorigenesis. |
| Databáze: | OpenAIRE |
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