Novel interaction between the M4 muscarinic acetylcholine receptor and elongation factor 1A2

被引:25
作者
McClatchy, DB
Knudsen, CR
Clark, BF
Kahn, RA
Hall, RA
Levey, AI
机构
[1] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Dept Neurol, Atlanta, GA 30322 USA
[2] Aarhus Univ, Inst Mol & Struct Biol, DK-8000 Aarhus C, Denmark
[3] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA
[4] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA
关键词
D O I
10.1074/jbc.M203081200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The activation of the muscarinic acetylcholine receptor (mAChR) family, consisting of five subtypes (M-1-M-5), produces a variety of physiological effects throughout the central nervous system. However, the role of each individual subtype remains poorly understood. To further elucidate signal transduction pathways for specific subtypes, we used the most divergent portion of the subtypes, the intracellular third (i3) loop, as bait to identify interacting proteins. Using a brain pull-down assay, we identify elongation factor 1A2 (eEF1A2) as a specific binding partner to the i3 loop of M-4, and not to M-1 or M-2. In addition, we demonstrate a direct interaction between these proteins. In the rat striatum, the M4 mAChR colocalizes with eEF1A2 in the soma and neuropil. In PC12 cells, endogenous eEF1A2 co-immunoprecipitates with the endogenous M4 mAChR, but not with the endogenous M, mAChR. In our in vitro model, M4 dramatically accelerates nucleotide exchange of eEF1A2, a GTP-binding protein. This indicates the M, mAChR is a guanine exchange factor for eEF1A2. eEF1A2 is an essential GTP-binding protein for protein synthesis. Thus, our data suggest a novel role for M4 in the regulation of protein synthesis through its interaction with eEF1A2.
引用
收藏
页码:29268 / 29274
页数:7
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