CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre
CAMSAP2 organizes a γ-tubulin-independent microtubule nucleation centre
复制标题
CAMSAP2 组织一个独立于 γ-微管蛋白的微管成核中心
DOI：
10.1101/2021.03.01.433304
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Nitta Ryo et al.
中科院分区：
文献类型：
--
作者：
Imasaki Tsuyoshi;Nitta Ryo et al.
微管是由αβ-微管蛋白异源二聚体组成的动态聚合物。最初的聚合过程称为微管成核，通过αβ-微管蛋白自发发生。由于大的能垒阻止细胞中的微管成核，因此γ-微管蛋白环复合物被募集到中心体以克服成核垒。然而，已知相当数量的微管从中心体脱离有助于细胞中的基本过程。在这里，我们提出的证据表明，负端结合钙调素调节血影蛋白相关蛋白2（CAMSAP 2）作为一个强大的成核剂微管形成可溶性αβ微管蛋白独立的γ-微管蛋白。CAMSAP 2通过稳定αβ-微管蛋白之间的纵向接触，显著降低成核屏障，接近微管聚合的临界浓度。CAMSAP 2与αβ-微管蛋白聚集在一起以产生成核中间体，许多微管从成核中间体辐射，形成紫菀样结构。我们的研究结果表明，CAMSAP 2支持微管的生长，组织成核中心，以及通过稳定微管成核中间体。
Microtubules are dynamic polymers consisting of αβ-tubulin heterodimers. The initial polymerization process, called microtubule nucleation, occurs spontaneously via αβ-tubulin. Since a large energy barrier prevents microtubule nucleation in cells, the γ-tubulin ring complex is recruited to the centrosome to overcome the nucleation barrier. However, detachment of a considerable number of microtubules from the centrosome is known to contribute to fundamental processes in cells. Here, we present evidence that minus-end-binding calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) serves as a strong nucleator for microtubule formation from soluble αβ-tubulin independent of γ-tubulin. CAMSAP2 significantly reduces the nucleation barrier close to the critical concentration for microtubule polymerization by stabilizing the longitudinal contacts among αβ-tubulins. CAMSAP2 clusters together with αβ-tubulin to generate nucleation intermediates, from which numerous microtubules radiate, forming aster-like structures. Our findings suggest that CAMSAP2 supports microtubule growth by organizing a nucleation centre as well as by stabilizing microtubule nucleation intermediates.