title: SLK-dependent activation of ERMs controls LGN-NuMA localization and spindle orientation.
abstract: Mitotic spindle orientation relies on a complex dialog between the spindle microtubules and the cell cortex, in which F-actin has been recently implicated. Here, we report that the membrane-actin linkers ezrin/radixin/moesin (ERMs) are strongly and directly activated by the Ste20-like kinase at mitotic entry in mammalian cells. Using microfabricated adhesive substrates to control the axis of cell division, we found that the activation of ERMs plays a key role in guiding the orientation of the mitotic spindle. Accordingly, impairing ERM activation in apical progenitors of the mouse embryonic neocortex severely disturbed spindle orientation in vivo. At the molecular level, ERM activation promotes the polarized association at the mitotic cortex of leucine-glycine-asparagine repeat protein (LGN) and nuclear mitotic apparatus (NuMA) protein, two essential factors for spindle orientation. We propose that activated ERMs, together with Gαi, are critical for the correct localization of LGN-NuMA force generator complexes and hence for proper spindle orientation.
authors: Membrane Traffic and Cell Division Laboratory, Institut Pasteur, 75015 Paris, France Centre National de la Recherche Scientifique URA2582, 75015 Paris, France Sorbonne Universités, Université Pierre et Marie Curie, Université Paris 06, Institut de formation doctorale, 75252 Paris, France.
authors: Mickael
authors: M
authors: Machicoane
authors: Institut de Biologie de L'Ecole Normale Supérieure, Ecole Normale Supérieure, 75005 Paris, France Institut National de la Santé et de la Recherche Médicale, U1024, Centre National de la Recherche Scientifique UMR8197, 75005 Paris, France.
authors: Cristina A
authors: CA
authors: de Frutos
authors: Systems Cell Biology of Cell Polarity and Cell Division Laboratory, Institut Curie, 75005 Paris, France Centre National de la Recherche Scientifique UMR144, 75005 Paris, France.
authors: Jenny
authors: J
authors: Fink
authors: Membrane Traffic and Cell Division Laboratory, Institut Pasteur, 75015 Paris, France Centre National de la Recherche Scientifique URA2582, 75015 Paris, France.
authors: Murielle
authors: M
authors: Rocancourt
authors: Membrane Traffic and Cell Division Laboratory, Institut Pasteur, 75015 Paris, France Centre National de la Recherche Scientifique URA2582, 75015 Paris, France.
authors: Yannis
authors: Y
authors: Lombardi
authors: Institut de Biologie de L'Ecole Normale Supérieure, Ecole Normale Supérieure, 75005 Paris, France Institut National de la Santé et de la Recherche Médicale, U1024, Centre National de la Recherche Scientifique UMR8197, 75005 Paris, France.
authors: Sonia
authors: S
authors: Garel
authors: Systems Cell Biology of Cell Polarity and Cell Division Laboratory, Institut Curie, 75005 Paris, France Centre National de la Recherche Scientifique UMR144, 75005 Paris, France.
authors: Matthieu
authors: M
authors: Piel
authors: Membrane Traffic and Cell Division Laboratory, Institut Pasteur, 75015 Paris, France Centre National de la Recherche Scientifique URA2582, 75015 Paris, France arnaud.echard@pasteur.fr.
authors: Arnaud
authors: A
authors: Echard
mesh_terms: D034961:Antigens, Nuclear / Q000032:analysis / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism*; D000099149:Ezrin; D000099317:Hippo Kinases
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D034521:Nuclear Matrix-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D000099149:Ezrin; C102754:GPSM2 protein, human; C050045:NUMA1 protein, human; C071058:moesin; C071776:radixin; C485733:SLK protein, human; D000099317:Hippo Kinases