Schneider-Brachert, Wulf and Tchikov, Vladimir and Neumeyer, Jens and Jakob, Marten and Winoto-Morbach, Supandi and Held-Feindt, Janka and Heinrich, Michael and Merkel, Oliver and Ehrenschwander, Martin and Adam, Dieter and Mentlein, Rolf and Kabelitz, Dieter and Schuetze, Stefan (2004) Compartmentalization of TNF receptor 1 signaling: Internalized TNF receptosomes as death signaling vesicles. IMMUNITY, 21 (3). pp. 415-428. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)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 DeltaTRID) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; NEUTRAL SPHINGOMYELINASE; ACID SPHINGOMYELINASE; INDUCED APOPTOSIS; COMPLEX DISC; RECEPTOR-1; PROTEIN; ACTIVATION; CASPASE-8; PATHWAY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jun 2021 06:55 |
| Last Modified: | 30 Jun 2021 06:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37243 |
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