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Elongation Factor 1A Family Regulates the Recycling of the M4 Muscarinic Acetylcholine Receptor

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Abstract

In this study, we tested the hypothesis that the elongation 1A (eEF1A) family regulates the cell surface density of the M4 subtype of the muscarinic acetylcholine receptors (mAChR) following agonist-induced internalization. Here, we show that mouse brains lacking eEF1A2 have no detectable changes in M4 expression or localization. We, however, did discover that eEF1A1, the other eEF1A isoform, is expressed in adult neurons contrary to previous reports. This novel finding suggested that the lack of change in M4 expression and distribution in brains lacking eEF1A2 might be due to compensatory effects of eEF1A1. Supporting this theory, we demonstrate that the overexpression of either eEF1A1 or eEF1A2 inhibits M4 recovery to the cell surface after agonist-induced internalization in PC12 cells. Furthermore, eEF1A1 or eEF1A2 had no effect on the recovery of the M1 subtype in PC12 cells. These results demonstrate the novel ability of the eEF1A family to specifically regulate the M4 mAChR.

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Acknowledgments

This work was supported by National Institutes of Health Grant RO1 NS30454 (A.I.L.) and National Institutes of Health NRSA fellowship (D.B.M.). We would like to thank Helen Newbery, Tatjana Paunesku, and Howard Rees for their technical assistance with the wasted brains and immunohistochemistry and Laura Volpicelli-Daley for her helpful discussions.

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Authors and Affiliations

  1. Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Rd, SR-11, La Jolla, CA, 92037, USA

    Daniel B. McClatchy

  2. Department of Neurology, Emory University, Atlanta, GA, USA

    Guofu Fang & Allan I. Levey

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  1. Daniel B. McClatchy
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  2. Guofu Fang
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Correspondence to Daniel B. McClatchy.

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McClatchy, D.B., Fang, G. & Levey, A.I. Elongation Factor 1A Family Regulates the Recycling of the M4 Muscarinic Acetylcholine Receptor. Neurochem Res 31, 975–988 (2006). https://doi.org/10.1007/s11064-006-9103-1

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