Evidence map›Paper›PMID 26276394›Full record

ArticleThe Journal of biological chemistry2015

Mechanisms of inhibition and potentiation of α4β2 nicotinic acetylcholine receptors by members of the Ly6 protein family.

Meilin Wu, Clare A Puddifoot, Palmer Taylor, William J Joiner

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
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  5. A novel anxiety-associated SNP identified inFrontiers in behavioral neuroscience · 2024
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  8. HumanOncotarget · 2023
    Article
  9. Xanomeline restores endogenous nicotinic acetylcholine receptor signaling in mouse prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Unbalanced Regulation of α7 nAChRs by Ly6h and NACHO Contributes to Neurotoxicity in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  15. Review
  16. Article
  17. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Meilin WuFrom the Department of Pharmacology.
Clare A PuddifootFrom the Department of Pharmacology.
Palmer TaylorFrom the Department of Pharmacology, Biomedical Sciences Graduate Program, Neuroscience Graduate Program, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0636.
William J JoinerFrom the Department of Pharmacology, Biomedical Sciences Graduate Program, Neuroscience Graduate Program, Center for Circadian Biology, and wjoiner@ucsd.edu.
University of California, San Diego · USCircadian (United States) · US

Funding

KINETICS OF DRUG-MACROMOLECULE COMPLEX FORMATIONR01GM018360 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, PALMER WILLIAM · 1985 to 2013
$2.8M
Molecular and anatomical basis of sleep regulation by SLEEPLESSR01NS072431 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOINER, WILLIAM J · 2011 to 2015
$1.7M
NIGMS NIH HHS R01 GM018360NIGMS NIH HHS R01 GM18360NINDS NIH HHS R01 NS072431
6 · The paper itself

Abstract

α4β2 nicotinic acetylcholine receptors (nAChRs) are abundantly expressed throughout the central nervous system and are thought to be the primary target of nicotine, the main addictive substance in cigarette smoking. Understanding the mechanisms by which these receptors are regulated may assist in developing compounds to selectively interfere with nicotine addiction. Here we report previously unrecognized modulatory properties of members of the Ly6 protein family on α4β2 nAChRs. Using a FRET-based Ca(2+) flux assay, we found that the maximum response of α4β2 receptors to agonist was strongly inhibited by Ly6h and Lynx2 but potentiated by Ly6g6e. The mechanisms underlying these opposing effects appear to be fundamentally distinct. Receptor inhibition by Lynx2 was accompanied by suppression of α4β2 expression at the cell surface, even when assays were preceded by chronic exposure of cells to an established chaperone, nicotine. Receptor inhibition by Lynx2 also was resistant to pretreatment with extracellular phospholipase C, which cleaves lipid moieties like those that attach Ly6 proteins to the plasma membrane. In contrast, potentiation of α4β2 activity by Ly6g6e was readily reversible by pretreatment with phospholipase C. Potentiation was also accompanied by slowing of receptor desensitization and an increase in peak currents. Collectively our data support roles for Lynx2 and Ly6g6e in intracellular trafficking and allosteric potentiation of α4β2 nAChRs, respectively.

Indexed as

Allosteric SiteAnimalsAntigens, LyBiotinylationCalciumCell MembraneFluorescence Resonance Energy TransferGreen Fluorescent ProteinsHEK293 CellsHumansLipidsMembrane GlycoproteinsMiceNeuropeptidesNicotineNicotinic AgonistsAntigens, LyCalciumGreen Fluorescent ProteinsLipidsLy6g6e protein, mouseLypd1 protein, mouseMembrane GlycoproteinsNeuropeptidesNicotineNicotinic Agonistsnicotinic receptor alpha4beta2Receptors, NicotinicType C PhospholipasesCys-loop receptorion channelLy6neurotransmitter receptornicotinenicotinic acetylcholine receptors (nAChR)receptor desensitizationα neurotoxin

Identifiers

PMID26276394
PMCPMC4591831
OpenAlexW2100529316

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.