Kim Youni, Lee Hyun-Kyung, Park Kyeong-Yeon, Ismail Tayaba, Lee Hongchan, Lee Hyun-Shik
KNU G-LAMP Project Group, KNU Institute of Basic Sciences, School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daegu 41566, Korea.
Dev Reprod. 2024 Sep;28(3):109-119. doi: 10.12717/DR.2024.28.3.109. Epub 2024 Sep 30.
The actin cytoskeleton plays fundamental roles in ciliogenesis and the actin depolymerizing factor destrin regulates actin dynamics by treadmilling actin filaments and increasing globular actin pools. However, the specific developmental roles of destrin in ciliogenesis have not been fully elucidated. Here, we investigated the function of destrin in ciliogenesis using and human retinal pigmented epithelial (hRPE1) cells. We discovered the loss of destrin increased the number of multiciliated cells in the epithelium and impeded cilia motility. Additionally, destrin depletion remarkably reduced the length of primary cilia in the neural tube and hRPE1 cells by affecting actin dynamics. Immunofluorescence using markers of ciliary components indicated that destrin controls the directionality and polarity of basal bodies and axonemal elongation by modulating actin dynamics, independent of basal body docking. In conclusion, destrin plays a significant role during vertebrate ciliogenesis regulating both primary and multicilia development. Our data suggest new insights for understanding the roles of actin dynamics in cilia development.
肌动蛋白细胞骨架在纤毛发生过程中发挥着重要作用,而肌动蛋白解聚因子destrin通过肌动蛋白丝的踏车行为和增加球状肌动蛋白池来调节肌动蛋白动力学。然而,destrin在纤毛发生过程中的具体发育作用尚未完全阐明。在这里,我们使用小鼠和人视网膜色素上皮(hRPE1)细胞研究了destrin在纤毛发生中的功能。我们发现destrin的缺失增加了小鼠上皮中多纤毛细胞的数量,并阻碍了纤毛的运动。此外,destrin的缺失通过影响肌动蛋白动力学显著缩短了小鼠神经管和hRPE1细胞中初级纤毛的长度。使用纤毛成分标记物的免疫荧光表明,destrin通过调节肌动蛋白动力学来控制基体的方向性和极性以及轴丝伸长,而与基体对接无关。总之,destrin在脊椎动物纤毛发生过程中发挥着重要作用,调节初级纤毛和多纤毛的发育。我们的数据为理解肌动蛋白动力学在纤毛发育中的作用提供了新的见解。