Human Nek7-interactor RGS2 is required for mitotic spindle organization

Autor(es)

de Souza, Edmarcia Elisa ^{[1, 2]} ; Hehnly, Heidi ^{[3, 4]} ; Perez, Arina Marina ^[1] ; Meirelles, Gabriela Vaz ^[1] ; Costa Smetana, Juliana Helena ^[1] ; Doxsey, Stephen ^[4] ; Kobarg, Joerg ^{[2, 5, 6]}

Afiliação do(s) autor(es)

^[1] CNPEM, LNBio, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Programa Posgrad Biol Func & Mol, Campinas, SP - Brazil

^[3] Univ Washington, Dept Pharmacol, Seattle, WA 98195 - USA

^[4] Univ Massachusetts, Sch Med, Program Mol Genet & Microbiol, Worcester, MA - USA

^[5] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP - Brazil

^[6] Univ Estadual Campinas, Fac Ciencias Farmaceut, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELL CYCLE; v. 14, n. 4, p. 656-667, FEB 15 2015.
• Citações Web of Science: 3

Resumo

The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced -tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization. (AU)

• Processo FAPESP: 10/51730-0 - SMolBNet 2.0: estudos funcionais e estruturais de proteína-cinases envolvidas em câncer e doenças negligenciadas, visando ao desenvolvimento de novos inibidores
• Beneficiário: Jörg Kobarg
• Modalidade de apoio: Auxílio à Pesquisa - Regular