1. Signal Transduction and Intracellular Trafficking by the Interleukin 36 Receptor
- Author
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Siddhartha S. Saha, Ernest L. Raymond, Joseph R. Woska, Christine Grimaldi, Gary O. Caviness, Su-Ellen Brown, Detlev Mennerich, M. Lamine Mbow, Divyendu Singh, Rajkumar Ganesan, and C. Cheng Kao
- Subjects
LAMP1 ,TOLLIP ,Immunology ,Intracellular Signaling Peptides and Proteins ,Receptors, Interleukin ,Cell Biology ,Receptor-mediated endocytosis ,Biology ,Endocytosis ,Biochemistry ,Cell Line ,Transport protein ,Cell biology ,Protein Transport ,Humans ,Signal transduction ,Lysosomes ,Receptor ,Molecular Biology ,Intracellular ,Interleukin-1 ,Signal Transduction - 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.
- Published
- 2015
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