Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands.
Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and The Netherlands Proteomics Centre, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands.
Dev Cell. 2014 Feb 10;28(3):295-309. doi: 10.1016/j.devcel.2014.01.001. Epub 2014 Jan 30.
Microtubules are cytoskeletal polymers with two structurally and functionally distinct ends, the plus- and the minus-end. Here, we focus on the mechanisms underlying the regulation of microtubule minus-ends by the CAMSAP/Nezha/Patronin protein family. We show that CAMSAP2 is required for the proper organization and stabilization of interphase microtubules and directional cell migration. By combining live-cell imaging and in vitro reconstitution of microtubule assembly from purified components with laser microsurgery, we demonstrate that CAMSAPs regulate microtubule minus-end growth and are specifically deposited on the lattice formed by microtubule minus-end polymerization. This process leads to the formation of CAMSAP-decorated microtubule stretches, which are stabilized from both ends and serve as sites of noncentrosomal microtubule outgrowth. The length of the stretches is regulated by the microtubule-severing protein katanin, which interacts with CAMSAPs. Our data thus indicate that microtubule minus-end assembly drives the stabilization of noncentrosomal microtubules and that katanin regulates this process.
微管是细胞骨架聚合物,具有两个结构和功能不同的末端,即正端和负端。在这里,我们专注于 CAMSAP/Nezha/Patronin 蛋白家族调节微管负端的机制。我们表明 CAMSAP2 是间期微管的适当组织和稳定以及定向细胞迁移所必需的。通过结合活细胞成像和从纯化成分体外重建微管组装与激光显微手术,我们证明 CAMSAPs 调节微管负端生长,并特异性沉积在微管负端聚合形成的晶格上。这个过程导致 CAMSAP 装饰的微管延伸的形成,这些延伸从两端稳定,并作为非中心体微管生长的位点。延伸的长度由微管切割蛋白katanin 调节,katanin 与 CAMSAPs 相互作用。因此,我们的数据表明微管负端组装驱动非中心体微管的稳定,并且katanin 调节这个过程。