(Verbatim from applicant?s abstract): Muscarinic acetylcholine receptors (mAChRs) have been implicated in a variety of brain disorders, including Alzheimer?s disease, Parkinson?s disease, and schizophrenia. Therefore, the study of mAChR will lead to a better understanding of complex neural processes and possible treatments for diseases. We have identified a novel interaction between elongation factor 1A2 (eEF1A2) and the M4 mAChR subtype. SA#1 We will characterize this interaction in rat brain using confocal microscopy and immunoprecipitations. SA#2 eEF1A2 is an actin binding protein (ABP) and other ABPs regulate the trafficking of GPCRs. We will test the hypothesis that eEF1A2 regulates M4 trafficking by generating a M4 mutant and examining its trafficking pathway compared to wild type M4 with confocal microscopy. SA#3 eEF1A2 is essential for translation and muscarinic activation can increase dendritic translation. eEFIA2 binding to nucleotides is crucial to translation and M4 regulates nucleotide binding of heterotrimeric Gi. We will test the hypothesis M4 regulates eEF1A2 activity by modulating its nucleotide binding via filter binding assays.
| McClatchy, Daniel B; Knudsen, Charlotte R; Clark, Brian F et al. (2002) Novel interaction between the M4 muscarinic acetylcholine receptor and elongation factor 1A2. J Biol Chem 277:29268-74 |
