贸易
时尚
细胞生物学
内化
生物
内吞作用
内体
内吞循环
肿瘤坏死因子α
信号转导
死亡域
受体
细胞凋亡
程序性细胞死亡
半胱氨酸蛋白酶
免疫学
细胞内
生物化学
作者
Wulf Schneider‐Brachert,Vladimir Tchikov,Jens Neumeyer,Marten Jakob,Supandi Winoto‐Morbach,Janka Held‐Feindt,Michael Heinrich,Oliver Merkel,Martin Ehrenschwender,Dieter Adam,Rolf Mentlein,Dieter Kabelitz,Stefan Schütze
出处
期刊:Immunity
[Elsevier]
日期:2004-09-01
卷期号:21 (3): 415-428
被引量:476
标识
DOI:10.1016/j.immuni.2004.08.017
摘要
Abstract
The molecular regulation of the recruitment of initial signaling complexes at the TNF-R1 is poorly defined. We demonstrate here that within minutes internalized TNF-R1 (TNF receptosomes) recruits TRADD, FADD, and caspase-8 to establish the "death-inducing signaling complex" (DISC). In addition, we identified the TNF-R1 internalization domain (TRID) required for receptor endocytosis and provide evidence that TNF-R1 internalization, DISC formation, and apoptosis are inseparable events. Analyzing cell lines expressing an internalization-deficient receptor (TNF-R1 ΔTRID) revealed that recruitment of RIP-1 and TRAF-2 to TNF-R1 occurred at the level of the plasma membrane. In contrast, aggregation of TRADD, FADD, and caspase-8 to establish the TNF-R1-associated DISC is critically dependent on receptor endocytosis. Furthermore, fusion of TNF receptosomes with trans-Golgi vesicles results in activation of acid sphingomyelinase and cathepsin D. Thus, TNF receptosomes establish the different TNF signaling pathways by compartmentalization of plasma membrane-derived endocytic vesicles harboring the TNF-R1-associated DISC.
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