New Muscarinic Acetylcholine Receptor Partner?

Science's STKE  13 Aug 2002:
Vol. 2002, Issue 145, pp. tw297-TW297
DOI: 10.1126/stke.2002.145.tw297

Muscarinic acetylcholine receptors (mAChR) have critical roles in the central nervous system and produce many of their effects by activating heterotrimeric guanine nucleotide-binding proteins. However, the five subtypes of muscarinic receptors (M1 through M5) produce distinct signals and thus may use other signaling mechanisms as well. McClatchy et al. screened for proteins that interact with the third intracellular loop portion of the M4 mAChR, a region that is highly variable between receptor subtypes. They identified elongation factor 1A2 (eEF1A2) as an interaction partner and showed that endogenous eEF1A2 could be coimmunoprecipitated with the M4 mAChR, but not the M1 mAChR, from cultured PC12 cells. The i3 loop acts as a guanine nucleotide exchange factor for receptor-coupled G proteins and the M4i3 loop also promoted nucleotide exchange on eEF1A2 in vitro. The eEF1A2 protein functions in control of translation and has other proposed functions as well. These functions are thus potentially regulated by M4 AChRs.

D. B. McClatchy, C. R. Knudsen, B. F. Clark, R. A. Kahn, R. A. Hall, A. I. Levey, Novel interaction between the M4 muscarinic acetylcholine receptor and elongation factor 1A2, J. Biol. Chem. 277, 29268-29274 (2002). [Abstract] [Full Text]