title: GAS2L1 Is a Centriole-Associated Protein Required for Centrosome Dynamics and Disjunction.
abstract: Mitotic spindle formation and chromosome segregation require timely separation of the two duplicated centrosomes, and this process is initiated in late G2 by centrosome disjunction. Here we report that GAS2L1, a microtubule- and actin-binding protein, associates with the proximal end of mature centrioles and participates in centriole dynamics and centrosome disjunction. GAS2L1 attaches microtubules and actin to centrosomes, and the loss of GAS2L1 inhibits centrosome disjunction in G2 and centrosome splitting induced by depletion of the centrosome linker rootletin. Conversely, GAS2L1 overexpression induces premature centrosome separation, and this activity requires GAS2L1 association with actin, microtubules, and the microtubule end-binding proteins. The centrosome-splitting effect of GAS2L1 is counterbalanced by rootletin, reflecting the opposing actions of GAS2L1 and the centrosome linker. Our work reveals a GAS2L1-mediated centriole-tethering mechanism of microtubules and actin, which provide the forces required for centrosome dynamics and separation.
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Franco K C
authors.initials: FK
authors.lastname: Au
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Bill K T
authors.initials: BK
authors.lastname: Hau
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Physics and Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Shengwang
authors.initials: S
authors.lastname: Du
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: qirz@ust.hk.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Qi
mesh_terms: D000199:Actins / Q000378:metabolism; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D021381:Protein Transport
chemical_list: D000199:Actins; C499237:CROCC protein, human; D003598:Cytoskeletal Proteins; C490934:GAS2L1 protein, human; D008840:Microfilament Proteins
keywords: GAS2L1; actin; centriole; centrosome; end-binding proteins; microtubules; plus-end-tracking proteins