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Cited by 430Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

Alternate stoichiometries of α4β2 nicotinic acetylcholine receptors

Nelson, Mark E, Kuryatov, Alexander, Choi, Catherine H, Zhou, Yan, Lindstrom, Jon·2003·Molecular Pharmacology
DOI 10.1124/mol.63.2.332
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Abstract

Two functional types of nicotinic acetylcholine receptors (nAChRs) are expressed when human embryonic kidney cells are permanently transfected with equal amounts of human alpha4 and beta2 subunit cDNAs. Most (82%) of these nAChRs exhibit an EC(50) of 74 +/- 6 microM for ACh, a much lower sensitivity than the remaining fraction (EC(50) of 0.7 +/- 0.4 microM) or than expected from expression of equal amounts of alpha4 and beta2 mRNAs in Xenopus laevis oocytes. We have found three conditions that can increase the number of nAChRs with high sensitivity to activation. These are: 1) transient transfection with additional beta2 subunits, 2) overnight incubation in nicotine, or 3) overnight culture at 29 degrees C. Using metabolic labeling with [(35)S]methionine to measure subunit stoichiometry, we found that the majority of nAChRs had a stoichiometry of (alpha4)(3)(beta2)(2). Overnight treatment with nicotine increased the number of nAChRs and increased the proportion of the (alpha4)(2)(beta2)(3) stoichiometry. Alternate alpha4beta2 nAChR stoichiometries with distinct functional properties raise the possibility for an interesting mode of synaptic regulation for nicotinic signaling in the mammalian brain.

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Crossref · 10.1124/mol.63.2.332

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  • Nicotine causes the preferential assembly of receptors with (α4)2(β2)3 stoichiometry.

    “Data from such favorable systems show that nicotine enhances the assembly of functional nAChRs containing the α4 and β2 subunits and also causes the preferential assembly of receptors with (α4)2(β2)3 stoichiometry (Buisson and Bertrand, 2001; Nelson et al., 2003; Kuryatov et al., 2005; Sallette et al., 2005; Vallejo et al., 2005; Son et al., 2009).”

    From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Nelson et al., 2003

  • Nicotine enhances the assembly of functional nAChRs containing the α4 and β2 subunits.

    “Data from such favorable systems show that nicotine enhances the assembly of functional nAChRs containing the α4 and β2 subunits and also causes the preferential assembly of receptors with (α4)2(β2)3 stoichiometry (Buisson and Bertrand, 2001; Nelson et al., 2003; Kuryatov et al., 2005; Sallette et al., 2005; Vallejo et al., 2005; Son et al., 2009).”

    From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Nelson et al., 2003

  • Nicotine is thought to increase the assembly of receptors with a (α4)2(β2)3 stoichiometry.

    “Because nicotine is thought to increase the assembly of receptors with a (α4)2(β2)3 stoichiometry (Nelson et al., 2003; Son et al., 2009)”

    From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Nelson et al., 2003

  • Chronic nicotine exposure shifts nAChR stoichiometry from approximately equal contributions of the two stoichiometries in nicotine-naive cells to ∼100% (α4)2(β2)3.

    “In fact, our experiments and previous data (Buisson and Bertrand, 2001; Nelson et al., 2003; Kuryatov et al., 2005; Sallette et al., 2005; Vallejo et al., 2005; Son et al., 2009) suggest a shift from approximately equal contributions of the two stoichiometries in nicotine-naive cells to ∼100% (α4)2(β2)3 after chronic nicotine exposure.”

    From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Nelson et al., 2003

  • Previous results based on glycosylation and molecular weight measures show that up-regulation is initiated in the ER.

    “These data correspond with previous results based on glycosylation and molecular weight measures, showing that up-regulation is initiated in the ER (Nelson et al., 2003; Kuryatov et al., 2005; Sallette et al., 2005).”

    From Nicotine up-regulates α4β2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning (2011) · cites this paper as Nelson et al., 2003

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Authors
Nelson, M. E., Kuryatov, A., Choi, C. H., Zhou, Y., & Lindstrom, J.
Affiliations
University of Pennsylvania (US)
ORCID
Venue
Molecular Pharmacology
Publisher
Elsevier BV
Published
2003-02
Volume
63
Issue
2
Pages
332-341
ISSN
0026-895X (ISSN-L)
DOI
10.1124/mol.63.2.332
OpenAlex
W2337946333
Semantic Scholar
dbb214d9298a2934b4b744d775aff014dcfae0be
Cited by
422
References
45
Citations by year
2026: 3 · 2025: 9 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 18 · 2019: 8 · 2018: 10 · 2017: 16 · 2016: 23 · 2015: 29 · 2014: 28 · 2013: 23 · 2012: 31
FWCI
6.32
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS011323)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
nicotinic acetylcholine receptors, subunit stoichiometry, acetylcholine sensitivity, nicotine, receptor maturation, transient transfection, temperature effects, human embryonic kidney cells
MeSH terms
Cells, Cultured, Humans, Receptors, Nicotinic, Temperature, Transfection, DNA, Complementary, Cholinergic Agonists, Protein Subunits

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