Nakamura Mitsutoshi, Parkhurst Susan M
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Cytoskeleton (Hoboken). 2025 Apr;82(4):229-233. doi: 10.1002/cm.21890. Epub 2024 Jun 22.
Individual cells have robust repair systems to survive cell cortex damage caused by mechanical and chemical stresses, allowing them to maintain the integrity of tissues and organs. The contraction of an actomyosin ring at the wound edge is a major mechanism for physically closing the cell wound. In contrast to polymerization and bundling of actin filaments, little is known about how linear actin filaments are bent to be integrated into the actin ring structure encircling the wound edge. We recently found that the five Drosophila Septins function simultaneously in the regulation of actomyosin ring assembly, contraction, and disassembly during cell wound repair. These Septins form two distinct complexes-Sep1-Sep2-Pnut and Sep4-Sep5-Pnut-composed of different subunits from the same groups. Strikingly, these two distinct Septin complexes have different degrees of F-actin bending activities that are consistent with their spatial recruitment: different degrees of curved actin filaments are required for the robust formation of different regions of the actomyosin ring. In addition, we found that the two Septin complexes are regulated by different molecular pathways as a loss of Anillin only affects Sep1-Sep2-Pnut complex recruitment. These findings open new directions for how individual Septin subunits form complexes and function differentially in cellular and developmental processes.
单个细胞拥有强大的修复系统,以在机械和化学应力导致的细胞皮层损伤中存活下来,从而使它们能够维持组织和器官的完整性。伤口边缘肌动球蛋白环的收缩是物理闭合细胞伤口的主要机制。与肌动蛋白丝的聚合和成束不同,关于线性肌动蛋白丝如何弯曲以整合到环绕伤口边缘的肌动蛋白环结构中,人们知之甚少。我们最近发现,果蝇的五种Septin蛋白在细胞伤口修复过程中,同时参与调节肌动球蛋白环的组装、收缩和拆卸。这些Septin蛋白形成两种不同的复合物——Sep1-Sep2-Pnut和Sep4-Sep5-Pnut——由同一组中的不同亚基组成。令人惊讶的是,这两种不同的Septin复合物具有不同程度的F-肌动蛋白弯曲活性,这与其空间募集情况一致:肌动球蛋白环不同区域的稳固形成需要不同程度的弯曲肌动蛋白丝。此外,我们发现这两种Septin复合物受不同分子途径的调控,因为Anillin的缺失仅影响Sep1-Sep2-Pnut复合物的募集。这些发现为单个Septin亚基如何形成复合物以及在细胞和发育过程中发挥不同功能开辟了新的方向。