Pitaval Amandine, Senger Fabrice, Letort Gaëlle, Gidrol Xavier, Guyon Laurent, Sillibourne James, Théry Manuel
UMR_S 1038, Biomics Lab, University Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Santé et de la Recherche, Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France.
UMR 5168, CytoMorpho Lab, University Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Recherche Agronomique, Centre National de la Recherche Scientifique, Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France.
J Cell Biol. 2017 Nov 6;216(11):3713-3728. doi: 10.1083/jcb.201610039. Epub 2017 Oct 9.
Primary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to the apical surface, yet surprisingly little is known about this initiating step. To gain insight into the mechanisms driving centrosome migration, we exploited the reproducibility of cell architecture on adhesive micropatterns to investigate the cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with the transient formation of an array of cold-stable microtubules, and actin cytoskeleton asymmetrical contraction participate in concert to drive apical centrosome migration. The distal appendage protein Cep164 appears to be a key actor involved in the cytoskeleton remodeling and centrosome migration, whereas intraflagellar transport 88's role seems to be restricted to axoneme elongation. Together, our data elucidate the hitherto unexplored mechanism of centrosome migration and show that it is driven by the increase and clustering of mechanical forces to push the centrosome toward the cell apical pole.
初级纤毛是位于细胞表面的感觉细胞器。它们的组装由中心体迁移至顶端表面启动,但令人惊讶的是,对于这一启动步骤知之甚少。为深入了解驱动中心体迁移的机制,我们利用粘附微图案上细胞结构的可重复性来研究支持其迁移的细胞骨架重塑。微管网络致密化和束集,伴随着一系列冷稳定微管的短暂形成,以及肌动蛋白细胞骨架的不对称收缩共同作用,驱动顶端中心体迁移。远端附属蛋白Cep164似乎是参与细胞骨架重塑和中心体迁移的关键因子,而鞭毛内运输蛋白88的作用似乎仅限于轴丝延长。总之,我们的数据阐明了迄今为止未被探索的中心体迁移机制,并表明它是由机械力的增加和聚集驱动,将中心体推向细胞顶端极。