title: The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle.
abstract: Kinetochore fibers (K-fibers) of the mitotic spindle are force-generating units that power chromosome movement during mitosis. K-fibers are composed of many microtubules that are held together throughout their length. Here, we show, using 3D electron microscopy, that K-fiber microtubules (MTs) are connected by a network of MT connectors. We term this network 'the mesh'. The K-fiber mesh is made of linked multipolar connectors. Each connector has up to four struts, so that a single connector can link up to four MTs. Molecular manipulation of the mesh by overexpression of TACC3 causes disorganization of the K-fiber MTs. Optimal stabilization of K-fibers by the mesh is required for normal progression through mitosis. We propose that the mesh stabilizes K-fibers by pulling MTs together and thereby maintaining the integrity of the fiber. Our work thus identifies the K-fiber meshwork of linked multipolar connectors as a key integrator and determinant of K-fiber structure and function.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, Coventry, United Kingdom.
authors.forename: Faye M
authors.initials: FM
authors.lastname: Nixon
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, Coventry, United Kingdom.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gutiérrez-Caballero
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Hood
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Booth
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Prior
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, Coventry, United Kingdom.
authors.forename: Stephen J
authors.identifier: http://orcid.org/0000-0001-8927-6967
authors.initials: SJ
authors.lastname: Royle
mesh_terms: D055032:Electron Microscope Tomography; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure*; D008938:Mitosis; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; C120551:TACC3 protein, human
keywords: cancer; cell biology; electron microscopy; human; microtubule; mitosis