Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
J Biol Chem. 2023 Nov;299(11):105340. doi: 10.1016/j.jbc.2023.105340. Epub 2023 Oct 12.
The unicellular protozoan Trypanosoma brucei has a single flagellum that is involved in cell motility, cell morphogenesis, and cell division. Inheritance of the newly assembled flagellum during the cell cycle requires its correct positioning, which depends on the faithful duplication or segregation of multiple flagellum-associated cytoskeletal structures, including the basal body, the flagellum attachment zone, and the hook complex. Along the flagellum attachment zone sites a set of four microtubules termed the microtubule quartet (MtQ), whose molecular function remains enigmatic. We recently reported that the MtQ-localized protein NHL1 interacts with the microtubule-binding protein TbSpef1 and regulates flagellum inheritance by promoting basal body rotation and segregation. Here, we identified a TbSpef1- and NHL1-associated protein named SNAP1, which co-localizes with NHL1 and TbSpef1 at the proximal portion of the MtQ, depends on TbSpef1 for localization and is required for NHL1 localization to the MtQ. Knockdown of SNAP1 impairs the rotation and segregation of the basal body, the elongation of the flagellum attachment zone filament, and the positioning of the newly assembled flagellum, thereby causing mis-placement of the cell division plane, a halt in cleavage furrow ingression, and an inhibition of cytokinesis completion. Together, these findings uncover a coordinating role of SNAP1 with TbSpef1 and NHL1 in facilitating flagellum positioning and cell division plane placement for the completion of cytokinesis.
单细胞原生动物布氏锥虫只有一根鞭毛，该鞭毛参与细胞运动、细胞形态发生和细胞分裂。在细胞周期中，新组装的鞭毛的遗传需要其正确定位，这取决于多个鞭毛相关细胞骨架结构的忠实复制或分离，包括基体、鞭毛附着区和钩复合体。鞭毛附着区沿线有一组称为微管四联体（MtQ）的四条微管，其分子功能仍然是个谜。我们最近报道称，MtQ 定位蛋白 NHL1 与微管结合蛋白 TbSpef1 相互作用，并通过促进基体旋转和分离来调节鞭毛遗传。在这里，我们鉴定了一个 TbSpef1 和 NHL1 相关的蛋白 SNAP1，它与 NHL1 和 TbSpef1 在 MtQ 的近端部分共定位，其定位依赖于 TbSpef1，并且是 NHL1 定位到 MtQ 所必需的。SNAP1 的敲低会损害基体的旋转和分离、鞭毛附着区丝状结构的延伸以及新组装的鞭毛的定位，从而导致细胞分裂平面的错位、分裂沟内陷的停止和胞质分裂的完成受到抑制。总之，这些发现揭示了 SNAP1 与 TbSpef1 和 NHL1 之间的协调作用，有助于鞭毛定位和细胞分裂平面的放置，以完成胞质分裂。
