The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention in Endothelial Cells

Abstract 222 Cytokines: Intracellular Signaling Platform, Tuesday, 5/4

Background: Vascular endothelial cells (ECs), a major target of TNF action, express both the 55kD (TNFR1) and 75kD (TNFR2) TNF receptors. Most of the effects of TNF, including gene activation and cell death, are mediated by TNFR1. A region of the intracellular portion of TNFR1 called the "death domain" (DD) recruits the adaptor protein TRADD to initiate TNF signal transduction. Although these interactions are thought to occur at the plasma membrane, TNFR1 in ECs is predominantly expressed in the Golgi apparatus. TNFR2 does not contain a DD and is more highly expressed on the cell surface. The relationship between receptor localization, structure, and function is not clear. We examined whether the DD, required for TNF signaling through TNFR1, is necessary for receptor localization.

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