PKU-THU Joint Center for Life Sciences, College of Life Sciences, School of Medical Sciences, Tsinghua University, Beijing 100084, China.
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Development. 2019 Jun 28;146(13):dev174615. doi: 10.1242/dev.174615.
The niche controls stem cell self-renewal and differentiation in animal tissues. Although the exocyst is known to be important for protein membrane trafficking and secretion, its role in stem cells and niches has never been reported. Here, this study shows that the exocyst functions in the niche to promote germline stem cell (GSC) progeny differentiation in the ovary by directly regulating EGFR membrane trafficking and signaling. Inactivation of exocyst components in inner germarial sheath cells, which form the differentiation niche, causes a severe GSC differentiation defect. The exocyst is required for maintaining niche cells and preventing BMP signaling in GSC progeny by promoting EGFR membrane targeting and signaling through direct association with EGFR. Finally, it is also required for EGFR membrane targeting, recycling and signaling in human cells. Therefore, this study reveals a novel function of the exocyst in niche cells to promote stem cell progeny differentiation by directly controlling EGFR membrane trafficking and signaling , and also provides important insight into how the niche controls stem cell progeny differentiation at the molecular level.
龛调控动物组织中的干细胞自我更新和分化。尽管外核蛋白复合物(exocyst)已知在蛋白质膜运输和分泌中起重要作用,但它在干细胞和龛中的作用从未被报道过。本研究表明,外核蛋白复合物在生殖干细胞(GSC)巢中发挥作用,通过直接调节 EGFR 膜运输和信号转导来促进生殖细胞的分化。在形成分化龛的内生殖鞘细胞中失活外核蛋白复合物成分,会导致 GSC 严重分化缺陷。外核蛋白复合物通过与 EGFR 直接结合,促进 EGFR 膜定位和信号转导,从而维持巢细胞并防止 GSC 后代中的 BMP 信号转导。最后,它对于 EGFR 膜靶向、循环和信号转导在人细胞中也是必需的。因此,这项研究揭示了外核蛋白复合物在龛细胞中的一个新功能,通过直接控制 EGFR 膜运输和信号转导来促进干细胞后代的分化,并为龛如何在分子水平上控制干细胞后代的分化提供了重要的见解。