de Souza Edmarcia Elisa, Hehnly Heidi, Perez Arina Marina, Meirelles Gabriela Vaz, Smetana Juliana Helena Costa, Doxsey Stephen, Kobarg Jörg
a Laboratório Nacional de Biociências-LNBio ; Centro Nacional de Pesquisa em Energia e Materiais-CNPEM ; Campinas , SP Brasil.
Cell Cycle. 2015;14(4):656-67. doi: 10.4161/15384101.2014.994988.
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 γ-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.
有丝分裂纺锤体装置由附着在动粒上的微管（MT）网络组成，而动粒由两个中心体（也称为纺锤体极）组织形成。除了这个中央纺锤体装置外，星状微管在有丝分裂纺锤体极组装并附着在细胞皮层上，以确保纺锤体的正确定向。我们提出，细胞周期相关激酶Nek7及其新的相互作用蛋白RGS2参与有丝分裂调控和纺锤体形成。我们发现RGS2以Nek7依赖的方式定位于有丝分裂纺锤体，并与Nek7一起对纺锤体形态和有丝分裂纺锤体极的完整性有贡献。RGS2的缺失导致有丝分裂延迟以及染色体排列和汇聚的严重缺陷。重要的是，RGS2或Nek7的缺失，甚至野生型或激酶失活的Nek7的过表达，都会使有丝分裂纺锤体极的γ-微管蛋白减少。除了导致有丝分裂延迟外，RGS2的缺失还会导致有丝分裂纺锤体定向错误，同时星状微管减少。我们提出，这些表型直接导致有丝分裂纺锤体与基质的对齐失败。总之，我们提出了一种分子机制，即Nek7和RGS2可能协同作用以确保有丝分裂纺锤体的正确组织。
