ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
The prototoxin LYPD6B modulates heteromeric α3β4-containing nicotinic acetylcholine receptors, but not α7 homomers.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Lypd6b depletion promotes CD8Nature communications · 2025Article
- Pro-Inflammatory Protein PSCA Is Upregulated in Neurological Diseases and Targets β2-Subunit-Containing nAChRs.Biomolecules · 2025Article
- 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
- Aβ1-42 Accumulation Accompanies Changed Expression of Ly6/uPAR Proteins, Dysregulation of the Cholinergic System, and Degeneration of Astrocytes in the Cerebellum of Mouse Model of Early Alzheimer Disease.International journal of molecular sciences · 2023Article
- HumanOncotarget · 2023Article
- Article
- Orientational Preferences of GPI-Anchored Ly6/uPAR Proteins.International journal of molecular sciences · 2022Article
- 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
- Dynamics and Interactions of GPI-Linked lynx1 Protein with/without Nicotinic Acetylcholine Receptor in Membrane Bilayers.The journal of physical chemistry. B · 2020Article
- Bioinformatic profiling identifies a platinum-resistant-related risk signature for ovarian cancer.Cancer medicine · 2020Article
- The α5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates α4β2Frontiers in synaptic neuroscience · 2020Review
- Article
- Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes.Frontiers in pharmacology · 2019Review
- Distinctive single-channel properties of α4β2-nicotinic acetylcholine receptor isoforms.PloS one · 2019Article
- Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: an update.British journal of pharmacology · 2018Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Prototoxins are a diverse family of membrane-tethered molecules expressed in the nervous system that modulate nicotinic cholinergic signaling, but their functions and specificity have yet to be completely explored. We tested the selectivity and efficacy of leukocyte antigen, PLAUR (plasminogen activator, urokinase receptor) domain-containing (LYPD)-6B on α3β4-, α3α5β4-, and α7-containing nicotinic acetylcholine receptors (nAChRs). To constrain stoichiometry, fusion proteins encoding concatemers of human α3, β4, and α5 (D and N variants) subunits were expressed in Xenopus laevis oocytes and tested with or without LYPD6B. We used the 2-electrode voltage-clamp method to quantify responses to acetylcholine (ACh): agonist sensitivity (EC50), maximal agonist-induced current (Imax), and time constant (τ) of desensitization. For β4-α3-α3-β4-α3 and β4-α3-β4-α3-α3, LYPD6B decreased EC50 from 631 to 79 μM, reduced Imax by at least 59%, and decreased τ. For β4-α3-α5D-β4-α3 and β4-α3-β4-α-α5D, LYPD6B decreased Imax by 63 and 32%, respectively. Thus, LYPD6B acted only on (α3)3(β4)2 and (α3)2(α5D)(β4)2 and did not affect the properties of (α3)2(β4)3, α7, or (α3)2(α5N)(β4)2 nAChRs. Therefore, LYPD6B acts as a mixed modulator that enhances the sensitivity of (α3)3(β4)2 nAChRs to ACh while reducing ACh-induced whole-cell currents. LYPD6B also negatively modulates α3β4 nAChRs that include the α5D common human variant, but not the N variant associated with nicotine dependence.
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