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Published on: July 26, 2017
Signal Transduction and Intracellular Trafficking by the Interleukin 36 Receptor
Siddhartha S Saha1, Divyendu Singh1, Ernest L Raymond2
1From the Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47401 and.
Abstract:
Improper signaling of the IL-36 receptor (IL-36R), a member of the IL-1 receptor family, has been associated with various inflammation-associated diseases. However, the requirements for IL-36R signal transduction remain poorly characterized. This work seeks to define the requirements for IL-36R signaling and intracellular trafficking. In the absence of cognate agonists, IL-36R was endocytosed and recycled to the plasma membrane. In the presence of IL-36, IL-36R increased accumulation in LAMP1+ lysosomes. Endocytosis predominantly used a clathrin-mediated pathway, and the accumulation of the IL-36R in lysosomes did not result in increased receptor turnover. The ubiquitin-binding Tollip protein contributed to IL-36R signaling and increased the accumulation of both subunits of the IL-36R.
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