CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression.
Histamine H3 receptor (H3R), one of G protein-coupled receptors (GPCRs), has been known to regulate neurotransmitter release negatively in central and peripheral nervous systems. Recently, a variety of intracellular proteins have been identified to interact with carboxy (C)-termini of GPCRs, and control their intracellular trafficking and signal transduction efficiencies. Screening for such proteins that interact with the C-terminus of H3R resulted in identification of one of the chloride intracellular channel (CLIC) proteins, CLIC4. The association of CLIC4 with H3R was confirmed in in vitro pull-down assays, coimmunoprecipitation from rat brain lysate, and immunofluorescence microscopy of rat cerebellar neurons. The data from flowcytometric analysis, radioligand receptor binding assay, and cell-based ELISA indicated that CLIC4 enhanced cell surface expression of wild-type H3R, but not a mutant form of the receptor that failed to interact with CLIC4. These results indicate that, by binding to the C-terminus of H3R, CLIC4 plays a critical role in regulation of the receptor cell surface expression.
Maeda
Kay
K
Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Haraguchi
Mitsuya
M
Kuramasu
Atsuo
A
Sato
Takeya
T
Ariake
Kyohei
K
Sakagami
Hiroyuki
H
Kondo
Hisatake
H
Yanai
Kazuhiko
K
Fukunaga
Kohji
K
Yanagisawa
Teruyuki
T
Sukegawa
Jun
J
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*
D018118:Chloride Channels; C467578:Clic4 protein, rat; D018100:Receptors, Histamine H3