Department of Biology, University of Saskatchewan, Saskatoon, Canada.
Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Sci Rep. 2023 Jun 9;13(1):9410. doi: 10.1038/s41598-023-36430-8.
The conserved Shugoshin (SGO) protein family is essential for mediating proper chromosome segregation from yeast to humans but has also been implicated in diverse roles outside of the nucleus. SGO's roles include inhibiting incorrect spindle attachment in the kinetochore, regulating the spindle assembly checkpoint (SAC), and ensuring centriole cohesion in the centrosome, all functions that involve different microtubule scaffolding structures in the cell. In Caenorhabditis elegans, a species with holocentric chromosomes, SGO-1 is not required for cohesin protection or spindle attachment but appears important for licensing meiotic recombination. Here we provide the first functional evidence that in C. elegans, Shugoshin functions in another extranuclear, microtubule-based structure, the primary cilium. We identify the centrosomal and microtubule-regulating transforming acidic coiled-coil protein, TACC/TAC-1, which also localizes to the basal body, as an SGO-1 binding protein. Genetic analyses indicate that TAC-1 activity must be maintained below a threshold at the ciliary base for correct cilia function, and that SGO-1 likely participates in constraining TAC-1 to the basal body by influencing the function of the transition zone 'ciliary gate'. This research expands our understanding of cellular functions of Shugoshin proteins and contributes to the growing examples of overlap between kinetochore, centrosome and cilia proteomes.
保守的 SGO（Shugoshin）蛋白家族对于从酵母到人介导正确的染色体分离是必不可少的，但也被牵连到细胞核外的各种作用。SGO 的作用包括抑制动粒中不正确的纺锤体附着，调节纺锤体组装检查点（SAC），并确保中心体中的中心粒黏合，所有这些功能都涉及细胞中不同的微管支架结构。在具有全染色体的秀丽隐杆线虫中，SGO-1 对于黏连蛋白保护或纺锤体附着不是必需的，但似乎对于有丝分裂重组的许可很重要。在这里，我们提供了第一个功能证据，表明在秀丽隐杆线虫中，Shugoshin 在另一个核外的、基于微管的结构中发挥作用，即初级纤毛。我们鉴定了中心体和微管调节转化酸性卷曲螺旋蛋白 TACC/TAC-1，它也定位于基体，作为 SGO-1 的结合蛋白。遗传分析表明，TAC-1 的活性必须在纤毛基部的一个阈值以下维持，以确保正确的纤毛功能，并且 SGO-1 可能通过影响过渡区“纤毛门”的功能来参与限制 TAC-1 到基体。这项研究扩展了我们对 Shugoshin 蛋白细胞功能的理解，并为动粒、中心体和纤毛蛋白质组之间的重叠提供了越来越多的例子。
