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A transmembrane motif governs the surface trafficking of nicotinic acetylcholine receptors

Nature Neuroscience volume 5, pages 963–970 (2002)Cite this article

Abstract

Surface expression of the nicotinic acetylcholine receptor (AChR) requires the assembly of multiple subunits in the endoplasmic reticulum (ER). Little is known, however, about the mechanism by which assembled receptor pentamers are transported to the cell membrane while unassembled subunits are retained in the ER. Here we report that a motif conserved in the transmembrane domain of AChR subunits is critically involved in this process. In COS cells, mutation within this signal allowed surface expression of unassembled subunits. Conversely, insertion of the sequence to unrelated proteins that are normally transported to the surface resulted in ER retention. The signal is buried in AChR pentamers, but is exposed on unassembled subunits in the ER, where it promotes protein degradation. We therefore conclude that this signal ensures surface trafficking of only functional AChRs.

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Figure 1: Surface expression of nicotinic AChR requires the assembly of multiple subunits into a pentamer.
Figure 2: The M1 domain prevents surface expression of unassembled AChR α subunits.
Figure 3: Proteins containing the M1 domain of the AChR α subunit are retained in the ER.
Figure 4: Molecular determinants that prevent surface expression of unassembled subunit.
Figure 5: The membrane signal confers retention to unrelated proteins and to the β, γ and δ subunits of the AChR.
Figure 6: The ER retention signal is buried in AChR pentamers, but is exposed on unassembled subunits and assembly intermediates.
Figure 7: The ER retention signal promotes protein degradation.

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Acknowledgements

This work was supported by National Institutes of Health grant RO1-NS38301 and the Muscular Dystrophy Association (Z.Z.W.). We thank E. Aizenman, Y.J. Liu and G.A. Herin for helpful discussions.

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  1. Department of Neurobiology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, 15261, Pennsylvania, USA

    Jun-Mei Wang, Lili Zhang, Yun Yao, Nitnara Viroonchatapan, Elizabeth Rothe & Zuo-Zhong Wang

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Wang, JM., Zhang, L., Yao, Y. et al. A transmembrane motif governs the surface trafficking of nicotinic acetylcholine receptors. Nat Neurosci 5, 963–970 (2002). https://doi.org/10.1038/nn918

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