The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling.
The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling.
复制标题
DOI：
10.1083/jcb.201709005
复制
发表时间：
2018-03-05
期刊：
影响因子：
--
通讯作者：
Zachos G
中科院分区：
文献类型：
--
作者：
Petsalaki E;Dandoulaki M;Zachos G
有丝分裂纺锤体检查点保护细胞免受染色体错误分离。Petsalaki等人表明，Chmp 4c（ESCRT复合物中的一种蛋白质）通过促进RZZ复合物定位于未连接的动粒，在调节纺锤体检查点信号传导方面具有令人惊讶的作用。有丝分裂纺锤体检查点延迟后期发作的存在下，未连接的动粒，和有效的检查点信号需要动粒定位的杆-ZW 10-Zwilch（RZZ）复合物。在本研究中，我们表明，人类Chmp 4c，一种蛋白质参与膜重塑，定位于着丝粒在前中期，但减少在中期板对齐的染色体。Chmp 4c促进稳定的着丝粒-微管附着，并且是适当的有丝分裂进程、忠实的染色体排列和分离所需的。Chmp 4c的消耗减少了RZZ和Mad 1-Mad 2检查点蛋白定位于前中期着丝粒，并在微管被诺考达唑解聚时损害有丝分裂阻滞。此外，Chmp 4c通过一个小的C-末端区域与ZW 10结合，组成型Chmp 4c着丝粒靶向导致ZW 10依赖性检查点中期阻滞。此外，Chmp 4c纺锤体功能不需要转运依赖性膜重塑所需的内体分选复合物。这些结果表明，Chmp 4c通过促进RZZ复合物定位于未连接的动粒来调节有丝分裂纺锤体检查点。
The mitotic spindle checkpoint protects cells against chromosome missegregation. Petsalaki et al. show that Chmp4c, a protein in the ESCRT complex, has a surprising role in regulating spindle checkpoint signaling by promoting localization of the RZZ complex to unattached kinetochores. The mitotic spindle checkpoint delays anaphase onset in the presence of unattached kinetochores, and efficient checkpoint signaling requires kinetochore localization of the Rod–ZW10–Zwilch (RZZ) complex. In the present study, we show that human Chmp4c, a protein involved in membrane remodeling, localizes to kinetochores in prometaphase but is reduced in chromosomes aligned at the metaphase plate. Chmp4c promotes stable kinetochore–microtubule attachments and is required for proper mitotic progression, faithful chromosome alignment, and segregation. Depletion of Chmp4c diminishes localization of RZZ and Mad1-Mad2 checkpoint proteins to prometaphase kinetochores and impairs mitotic arrest when microtubules are depolymerized by nocodazole. Furthermore, Chmp4c binds to ZW10 through a small C-terminal region, and constitutive Chmp4c kinetochore targeting causes a ZW10-dependent checkpoint metaphase arrest. In addition, Chmp4c spindle functions do not require endosomal sorting complex required for transport–dependent membrane remodeling. These results show that Chmp4c regulates the mitotic spindle checkpoint by promoting localization of the RZZ complex to unattached kinetochores.
登录
查看更多内容
影响因子：
21.3
作者：
Basto, R;Gomes, R;Karess, RE
通讯作者：
Karess, RE
影响因子：
7.5
作者：
Campsteijn, Coen;Vietri, Marina;Stenmark, Harald
通讯作者：
Stenmark, Harald
DOI：
10.1083/jcb.201311113
发表时间：
2014-03-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ballister ER;Riegman M;Lampson MA
通讯作者：
Lampson MA
影响因子：
9.2
作者：
Famulski, Jakub K.;Chan, Gordon K.
通讯作者：
Chan, Gordon K.
影响因子：
3.3
作者：
Kasuboski JM;Bader JR;Vaughan PS;Tauhata SB;Winding M;Morrissey MA;Joyce MV;Boggess W;Vos L;Chan GK;Hinchcliffe EH;Vaughan KT
通讯作者：
Vaughan KT