Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA; Group of Cell Motility and Muscle Contraction, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Curr Biol. 2020 Jun 22;30(12):2386-2394.e4. doi: 10.1016/j.cub.2020.04.035. Epub 2020 May 7.
Septins form rod-shaped hetero-oligomeric complexes that assemble into filaments and other higher-order structures, such as rings or hourglasses, at the cell division site in fungal and animal cells [1-4] to carry out a wide range of functions, including cytokinesis and cell morphogenesis. However, the architecture of septin higher-order assemblies and their control mechanisms, including regulation by conserved kinases [5, 6], remain largely unknown. In the budding yeast Saccharomyces cerevisiae, the five mitotic septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1) localize to the bud neck and form an hourglass before cytokinesis that acts as a scaffold for proteins involved in multiple processes as well as a membrane-diffusible barrier between the mother and developing bud [7-9]. The hourglass is remodeled into a double ring that sandwiches the actomyosin ring at the onset of cytokinesis [10-13]. How septins are assembled into a highly ordered hourglass structure at the division site [13] is largely unexplored. Here we show that the LKB1-like kinase Elm1, which has been implicated in septin organization [14], cell morphogenesis [15], and mitotic exit [16, 17], specifically associates with the septin hourglass during the cell cycle and controls hourglass assembly and stability, especially for the daughter half, by regulating filament pairing and the functionality of its substrate, the septin-binding protein Bni5. This study illustrates how a protein kinase regulates septin architecture at the filament level and suggests that filament pairing is a highly regulated process during septin assembly and remodeling in vivo.
septins 形成棒状异源寡聚复合物，在真菌和动物细胞的细胞分裂部位组装成纤维和其他高级结构，如环或沙漏，以执行广泛的功能，包括胞质分裂和细胞形态发生[1-4]。然而， septin 高级组装的结构及其控制机制，包括保守激酶的调节[5,6]，在很大程度上仍然未知。在出芽酵母酿酒酵母中，五个有丝分裂 septin（Cdc3、Cdc10、Cdc11、Cdc12 和 Shs1）定位于芽颈，并在胞质分裂前形成沙漏，作为参与多种过程的蛋白质的支架，以及母细胞和发育芽之间的膜扩散屏障[7-9]。沙漏被重塑成一个双环，在胞质分裂开始时夹在肌动球蛋白环上[10-13]。 septin 如何在分裂部位组装成高度有序的沙漏结构[13]在很大程度上尚未探索。在这里，我们表明 LKB1 样激酶 Elm1 参与 septin 组织[14]、细胞形态发生[15]和有丝分裂退出[16,17]，它在细胞周期中与 septin 沙漏特异性相关，并通过调节细丝配对及其底物 septin 结合蛋白 Bni5 的功能来控制沙漏组装和稳定性，特别是对女儿半体。这项研究说明了蛋白激酶如何在丝状体水平上调节 septin 结构，并表明细丝配对是 septin 在体内组装和重塑过程中高度调控的过程。
