ArticleJournal of neurochemistry2016
Functional interaction between Lypd6 and nicotinic acetylcholine receptors.
Article in Journal of neurochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Single-Cell Profiling of the Developing Organ of Corti Identifies Etv4/5/1 as Key Regulators of Pillar Cell Identity.bioRxiv : the preprint server for biology · 2026Article
- In Search of the Role of Three-Finger Starfish Proteins.Marine drugs · 2024Article
- Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline.Cell death discovery · 2024Article
- HumanOncotarget · 2023Article
- Article
- New Three-Finger Protein from StarfishMarine drugs · 2022Article
- Human Three-Finger Protein Lypd6 Is a Negative Modulator of the Cholinergic System in the Brain.Frontiers in cell and developmental biology · 2021Article
- Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors.International journal of molecular sciences · 2020Article
- Modulation of cholinergic activity through lynx prototoxins: Implications for cognition and anxiety regulation.Neuropharmacology · 2020Review
- Activation of Somatostatin Interneurons by Nicotinic Modulator Lypd6 Enhances Plasticity and Functional Recovery in the Adult Mouse Visual Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Article
- Evolution and Medical Significance of LU Domain-Containing Proteins.International journal of molecular sciences · 2019Review
- Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes.Frontiers in pharmacology · 2019Review
- Article
- Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: an update.British journal of pharmacology · 2018Review
- Occupational exposure to pesticides is associated with differential DNA methylation.Occupational and environmental medicine · 2018Article
- Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans.Molecular biology and evolution · 2018Article
- Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex.Neuroscience · 2017Article
- Does Epileptiform Activity Represent a Failure of Neuromodulation to Control Central Pattern Generator-Like Neocortical Behavior?Frontiers in neural circuits · 2017Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain-containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross-linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane-bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine-induced hippocampal inward currents in rat brain slices and decreases nicotine-induced extracellular signal-regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR-mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post-natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine-induced ERK phosphorylation and attenuates nicotine-induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.