Cited by 200Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

Novel Modulation of Neuronal Nicotinic Acetylcholine Receptors by Association with the Endogenous Prototoxin lynx1

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Ibañez-Tallon, Inés, Miwa, Julie M, Wang, Hai-Long, Adams, Niels C, Crabtree, Gregg W, Sine, Steven M, Heintz, Nathaniel·2002·Neuron

Abstract

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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Crossref · 10.1016/s0896-6273(02)00632-3

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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
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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