title: Cep72 regulates the localization of key centrosomal proteins and proper bipolar spindle formation.
abstract: Microtubule-nucleation activity and structural integrity of the centrosome are critical for various cellular functions. The gamma-tubulin ring complexes (gammaTuRCs) localizing to the pericentriolar matrix (PCM) of the centrosome are major sites of microtubule nucleation. The PCM is thought to be created by two cognate large coiled-coil proteins, pericentrin/kendrin and CG-NAP/AKAP450, and its stabilization by Kizuna is essential for bipolar spindle formation. However, the mechanisms by which these proteins are recruited and organized into a proper structure with microtubule-organizing activity are poorly understood. Here we identify a centrosomal protein Cep72 as a Kizuna-interacting protein. Interestingly, Cep72 is essential for the localization of CG-NAP and Kizuna. Cep72 is also involved in gammaTuRC recruitment to the centrosome and CG-NAP confers the microtubule-nucleation activity on the gammaTuRCs. During mitosis, Cep72-mediated microtubule organization is important for converging spindle microtubules to the centrosomes, which is needed for chromosome alignment and tension generation between kinetochores. Our findings show that Cep72 is the key protein essential for maintaining microtubule-organizing activity and structural integrity of the centrosome.
authors.affiliation: Division of Oncology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshimori
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Miho
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018385:Centrosome / Q000737:chemistry*; D002842:Chromatids / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008938:Mitosis; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; C542475:CEP72 protein, human; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D014404:Tubulin