The exocyst functions in niche cells to promote germline stem cell differentiation by directly controlling EGFR membrane trafficking
The exocyst functions in niche cells to promote germline stem cell differentiation by directly controlling EGFR membrane trafficking
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胞外囊在微环境细胞中发挥作用，通过直接控制 EGFR 膜运输来促进生殖干细胞分化
DOI：
10.1242/dev.174615
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发表时间：
2019-07-01
期刊：
影响因子：
4.6
通讯作者：
Xie, Ting
中科院分区：
文献类型：
--
作者：
Mao, Ying;Tu, Renjun;Xie, Ting
摘要动物组织中干细胞的自我更新和分化受微生态位的控制。虽然已知外囊对于蛋白质膜运输和分泌是重要的，但其在干细胞和壁龛中的作用从未被报道过。在这里，这项研究表明，外囊的功能，在生态位，以促进生殖系干细胞（GSC）的后代分化，在果蝇卵巢直接调节表皮生长因子受体膜的运输和信号。形成分化生态位的内生殖鞘细胞中的外囊成分失活会导致严重的GSC分化缺陷。外囊是维持小生境细胞和通过促进EGFR膜靶向和通过与EGFR直接缔合的信号传导来防止GSC后代中的BMP信号传导所必需的。最后，它也是人类细胞中EGFR膜靶向、再循环和信号传导所必需的。因此，本研究揭示了niche细胞中的exocyst在体内通过直接控制EGFR膜的运输和信号传导来促进干细胞后代分化的新功能，也为niche如何在分子水平上控制干细胞后代分化提供了重要的见解。总结：外囊直接控制果蝇和人类细胞中EGFR膜的运输、再循环和活化，并且在小生境中需要通过调节EGFR信号传导来促进生殖系干细胞分化。
ABSTRACT 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 Drosophila 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 in vivo, and also provides important insight into how the niche controls stem cell progeny differentiation at the molecular level. Summary: The exocyst directly controls EGFR membrane trafficking, recycling and activation in Drosophila and human cells, and is required in the niche to promote germline stem cell differentiation by regulating EGFR signaling.