期刊
DEVELOPMENT
卷 148, 期 15, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.196345
关键词
Exocyst complex; Germline stem cells; Notch; Intracellular trafficking; Par proteins
资金
- Wellcome Trust DBT India Alliance fellowship [IA/E/13/1/501]
- Regional Centre for Biotechnology (Pali, India)
- Regional Centre for Biotechnology, the Department of Biotechnology, Ministry of Science and Technology, India [BT/PR6420/GBD/27/435/2012]
- Science and Engineering Research Board [EMR/2016/007842]
- University Grants Commission
The study demonstrates that the exocyst complex regulates germline stem cell proliferation by modulating Notch signaling autonomously in the nematode Caenorhabditis elegans. Additionally, the exocyst complex interacts with other cellular components to maintain optimal membrane Notch levels and is required for Notch plasma membrane localization and signaling in mammalian cells.
The conserved exocyst complex regulates plasma membrane-directed vesicle fusion in eukaryotes. However, its role in stem cell proliferation has not been reported. Germline stem cell (GSC) proliferation in the nematode Caenorhabditis elegans is regulated by conserved Notch signaling. Here, we reveal that the exocyst complex regulates C. elegans GSC proliferation by modulating Notch signaling cell autonomously. Notch membrane density is asymmetrically maintained on GSCs. Knockdown of exocyst complex subunits or of the exocyst-interacting GTPases Rab5 and Rab11 leads to Notch redistribution from the GSC-niche interface to the cytoplasm, suggesting defects in plasma membrane Notch deposition. The anterior polarity (aPar) protein Par6 is required for GSC proliferation, and for maintaining niche-facing membrane levels of Notch and the exocyst complex. The exocyst complex biochemically interacts with the aPar regulator Par5 (14-3-3 zeta) and Notch in C. elegans and human cells. Exocyst components are required for Notch plasma membrane localization and signaling in mammalian cells. Our study uncovers a possibly conserved requirement of the exocyst complex in regulating GSC proliferation and in maintaining optimal membrane Notch levels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据