The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor.
The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor.
复制标题
DOI：
10.7554/elife.78201
复制
发表时间：
2022-06-15
期刊：
影响因子：
7.7
通讯作者：
DeSantis, Morgan E.
中科院分区：
文献类型：
--
作者：
Agrawal, Ritvija;Gillies, John P.;Zang, Juliana L.;Zhang, Jingjing;Garrott, Sharon R.;Shibuya, Hiroki;Nandakumar, Jayakrishnan;DeSantis, Morgan E.
动力蛋白利用ATP水解在多种生物环境中移动微管上的货物。动力蛋白在减数分裂中通过移动束缚在核膜上的染色体来促进配子发生所必需的同源配对，从而遇到了一个独特的挑战。虽然进行性动力蛋白运动需要结合到一个激活适配器，动力蛋白移动减数分裂染色体所需的激活适配器的身份是未知的。我们发现，减数分裂特异性核包膜蛋白KASH5是一个动力蛋白激活适配器：KASH5直接结合动力蛋白使用激活适配器之间的保守机制，并将动力蛋白转化为一个进行马达。我们映射KASH5的动力蛋白结合表面，识别在体外废除动力蛋白结合的突变，并在体内破坏培养细胞和小鼠精母细胞核膜中动力蛋白机械的募集。我们的研究确定KASH5作为第一个跨膜动力蛋白激活适配器，并提供了在减数分裂过程中它如何激活动力蛋白的分子见解。
Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.