Signal Transduction and Intracellular Trafficking by the Interleukin 36 Receptor.
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.
From the Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47401 and.
Siddhartha S
SS
Saha
From the Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47401 and.
Divyendu
D
Singh
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Ernest L
EL
Raymond
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Rajkumar
R
Ganesan
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Gary
G
Caviness
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Christine
C
Grimaldi
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Joseph R
JR
Woska
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Detlev
D
Mennerich
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877.
Su-Ellen
SE
Brown
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877 lamine.mbow@boehringer-ingelheim.com.
M Lamine
ML
Mbow
From the Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47401 and ckao@indiana.edu.
C Cheng
CC
Kao
D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D018123:Receptors, Interleukin; C410602:TOLLIP protein, human; C572887:interleukin 36, human; C571244:interleukin-36 receptor, human
IL-1; Tollip; endocytosis; immunology; interleukin 36 receptor; signal transduction; trafficking