title: Direct Microtubule-Binding by Myosin-10 Orients Centrosomes toward Retraction Fibers and Subcortical Actin Clouds.
abstract: Positioning of centrosomes is vital for cell division and development. In metazoan cells, spindle positioning is controlled by a dynamic pool of subcortical actin that organizes in response to the position of retraction fibers. These actin "clouds" are proposed to generate pulling forces on centrosomes and mediate spindle orientation. However, the motors that pull astral microtubules toward these actin structures are not known. Here, we report that the unconventional myosin, Myo10, couples actin-dependent forces from retraction fibers and subcortical actin clouds to centrosomes. Myo10-mediated centrosome positioning requires its direct microtubule binding. Computational image analysis of large microtubule populations reveals a direct effect of Myo10 on microtubule dynamics and microtubule-cortex interactions. Myo10's role in centrosome positioning is distinct from, but overlaps with, that of dynein. Thus, Myo10 plays a key role in integrating the actin and microtubule cytoskeletons to position centrosomes and mitotic spindles.
authors.affiliation: Department of Pediatric Oncology, Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: mijung_kwon@dfci.harvard.edu.
authors.forename: Mijung
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Bagonis
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
authors.affiliation: Department of Pediatric Oncology, Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: david_pellman@dfci.harvard.edu.
authors.forename: David
authors.initials: D
authors.lastname: Pellman
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C498718:MYO10 protein, human; D034741:RNA, Small Interfering; D053778:Thiazolidines; D009218:Myosins; D004398:Dyneins; C037067:latrunculin A