期刊
JOURNAL OF CELL BIOLOGY
卷 176, 期 4, 页码 445-458出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200609014
关键词
-
类别
资金
- NCI NIH HHS [P30 CA016042, CA16042] Funding Source: Medline
- NIAID NIH HHS [P30 AI028697, AI28697] Funding Source: Medline
- NIBIB NIH HHS [F31 EB006278] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007185, GM07185] Funding Source: Medline
- NINDS NIH HHS [NS049084, NS31885, R01 NS031885, R37 NS031885, R21 NS049084] Funding Source: Medline
Cleavage of Notch by furin is required to generate a mature, cell surface heterodimeric receptor that can be proteolytically activated to release its intracellular domain, which functions in signal transduction. Current models propose that ligand binding to heterodimeric Notch (hNotch) induces a disintegrin and metalloprotease (ADAM) proteolytic release of the Notch extracellular domain (NECD), which is subsequently shed and/or endocytosed by DSL ligand cells. We provide evidence for NECD release and internalization by DSL ligand cells, which, surprisingly, did not require ADAM activity. However, losses in either hNotch formation or ligand endocytosis significantly decreased NECD transfer to DSL ligand cells, as well as signaling in Notch cells. Because endocytosis-defective ligands bind hNotch, but do not dissociate it, additional forces beyond those produced through ligand binding must function to disrupt the intramolecular interactions that keep hNotch intact and inactive. Based on our findings, we propose that mechanical forces generated during DSL ligand endocytosis function to physically dissociate hNotch, and that dissociation is a necessary step in Notch activation.
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