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Novel Modulation of Neuronal Nicotinic Acetylcholine Receptors by Association with the Endogenous Prototoxin lynx1
Open accessAbstract
We previously identified lynx1 as a neuronal membrane molecule related to snake alpha-neurotoxins able to modulate nAChRs. Here, we show that lynx1 colocalizes with nAChRs on CNS neurons and physically associates with nAChRs. Single-channel recordings show that lynx1 promotes the largest of three current amplitudes elicited by ACh through alpha(4)beta(2) nAChRs and that lynx1 enhances desensitization. Macroscopic recordings quantify the enhancement of desensitization onset by lynx1 and further show that it slows recovery from desensitization and increases the EC(50). These experiments establish that direct interaction of lynx1 with nAChRs can result in a novel type of functional modulation and suggest that prototoxins may play important roles in vivo by modulating functional properties of their cognate CNS receptors.
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“In the presence of lynx1, α4β2 nAChRs are up to 20-fold less sensitive to ACh in a Xenopus oocyte expression system, desensitize more rapidly, and recover more slowly from desensitization (114).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [114]
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Self-citation
Metadata
- Authors
- Ibañez-Tallon, I., Miwa, J. M., Wang, H.-L., Adams, N. C., Crabtree, G. W., Sine, S. M., & Heintz, N.
- Affiliations
- Howard Hughes Medical Institute (US)
- Mayo Clinic (US)
- Rockefeller University (US)
- Columbia University (US)
- Corresponding author
- Heintz, Nathaniel
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 33
- Issue
- 6
- Pages
- 893-903
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1966246536
- Cited by
- 200
- References
- 43
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 13 · 2019: 4 · 2018: 5 · 2017: 11 · 2016: 12 · 2015: 14 · 2014: 12 · 2013: 7 · 2012: 10
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4156 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2p01ns030532-06a1)
- National Cancer Institute (CA 09673, T32CA009673)
- National Institute of Neurological Disorders and Stroke (P01 NS 30532, NS 31744, NS22061, R01NS022061)
- 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
- Lynx1, neuronal nicotinic acetylcholine receptors, alpha4beta2 nAChR, receptor desensitization, receptor modulation, ligand-gated ion channels, central nervous system neurons
- MeSH terms
- Acetylcholine, Animals, Cell Line, Humans, Immunohistochemistry, Membrane Glycoproteins, Neurons, Neuropeptides, Oocytes, Receptors, GABA-A, Receptors, Nicotinic, Transfection, Vasodilator Agents, Xenopus laevis, Protein Structure, Tertiary, Patch-Clamp Techniques, Protein Subunits, Adaptor Proteins, Signal Transducing, GPI-Linked Proteins
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