Kanfer Gil, Peterka Martin, Arzhanik Vladimir K, Drobyshev Alexei L, Ataullakhanov Fazly I, Volkov Vladimir A, Kornmann Benoît
Institute of Biochemistry, ETH Zurich, ZH 8093 Zurich, Switzerland.
Department of Bioengineering and Bioinformatics, Moscow State University, 119991 Moscow, Russia.
Mol Biol Cell. 2017 Sep 1;28(18):2400-2409. doi: 10.1091/mbc.E16-11-0756. Epub 2017 Jul 12.
Dynamic microtubule ends exert pulling and pushing forces on intracellular membranes and organelles. However, the mechanical linkage of microtubule tips to their cargoes is poorly understood. CENP-F is a nonmotor microtubule-binding protein that participates in microtubule binding at kinetochores and in the mitotic redistribution of the mitochondrial network. CENP-F-driven mitochondrial transport is linked to growing microtubule tips, but the underlying molecular mechanisms are unknown. Here we show that CENP-F tracks growing microtubule ends in living cells. In vitro reconstitution demonstrates that microtubule tips can transport mitochondria and CENP-F-coated artificial cargoes over micrometer-long distances during both growing and shrinking phases. Based on these and previous observations, we suggest that CENP-F might act as a transporter of mitochondria and other cellular cargoes by attaching them to dynamic microtubule ends during both polymerization and depolymerization of tubulin.
动态微管末端对细胞内膜和细胞器施加拉力和推力。然而,微管末端与其货物之间的机械连接却鲜为人知。着丝粒蛋白F(CENP-F)是一种非马达微管结合蛋白,参与动粒处的微管结合以及线粒体网络的有丝分裂重新分布。CENP-F驱动的线粒体运输与正在生长的微管末端相关,但潜在的分子机制尚不清楚。在这里,我们表明CENP-F在活细胞中追踪正在生长的微管末端。体外重建表明,在微管的生长和收缩阶段,微管末端都能将线粒体和CENP-F包被的人工货物运输微米级的长距离。基于这些以及之前的观察结果,我们认为CENP-F可能通过在微管蛋白聚合和解聚过程中将线粒体和其他细胞货物附着到动态微管末端,从而充当它们的运输器。