Actin Depolymerizing Factor Destrin Regulates Cilia Development and Function during Vertebrate Embryogenesis.

Development & reproduction Pub Date : 2024-09-01 Epub Date: 2024-09-30 DOI:10.12717/DR.2024.28.3.109
Youni Kim, Hyun-Kyung Lee, Kyeong-Yeon Park, Tayaba Ismail, Hongchan Lee, Hyun-Shik Lee
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Abstract

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 Xenopus laevis and human retinal pigmented epithelial (hRPE1) cells. We discovered the loss of destrin increased the number of multiciliated cells in the Xenopus epithelium and impeded cilia motility. Additionally, destrin depletion remarkably reduced the length of primary cilia in the Xenopus 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.

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肌动蛋白解聚因子Destrin在脊椎动物胚胎发生过程中调控纤毛的发育和功能
肌动蛋白细胞骨架在纤毛发生过程中发挥着重要作用,肌动蛋白解聚因子去蛋白通过踩踏肌动蛋白丝和增加球状肌动蛋白池来调节肌动蛋白动力学。然而,去蛋白在纤毛发生中的具体发育作用尚未完全阐明。在这里,我们利用爪蟾和人类视网膜色素上皮细胞(hRPE1)研究了去甲肾上腺素在纤毛生成过程中的功能。我们发现,去甲肾上腺素的缺失增加了爪蟾上皮细胞中多纤毛细胞的数量,并阻碍了纤毛的运动。此外,通过影响肌动蛋白的动力学,去甲肾上腺素的缺失明显减少了爪蟾神经管和hRPE1细胞中初级纤毛的长度。使用纤毛成分标记物进行的免疫荧光表明,去甲肾上腺素通过调节肌动蛋白的动态来控制基底体的方向性和极性以及轴突的伸长,而与基底体的对接无关。总之,去甲肾上腺素在脊椎动物纤毛发生过程中发挥着重要作用,调控着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视角。
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