Evidence map›Paper›PMID 22949846›Full record

ArticleInternational journal of molecular sciences2012

Förster resonance energy transfer (FRET) correlates of altered subunit stoichiometry in cys-loop receptors, exemplified by nicotinic α4β2.

Rahul Srinivasan, Christopher I Richards, Crystal Dilworth, Fraser J Moss, Dennis A Dougherty, Henry A Lester

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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

19 citing papers in PubMed.

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  18. Discriminating between 5-HT₃A and 5-HT₃AB receptors.British journal of pharmacology · 2013
    Review
  19. Article
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

6 authors.

Rahul SrinivasanDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Christopher I RichardsDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Crystal DilworthDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Fraser J MossDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Dennis A DoughertyDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Henry A LesterDivision of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Funding

Alpha4 Nicotinic Receptor in Addiction: Mouse ModelsR01DA017279 · NIDA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2004 to 2014
$3.5M
NICOTINIC SYNAPSES, BIOPHYSICAL STUDIESR01NS011756 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 1985 to 2009
$3.4M
PROBING RECEPTOR STRUCTURES WITH UNNATURAL AMINO ACIDSR01NS034407 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DOUGHERTY, DENNIS A · 1995 to 2016
$3.1M
Probing Receptor Structures with Unnatural Amino AcidsR37NS034407 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI DOUGHERTY, DENNIS A · 2004 to 2010
$2.7M
Chronic nicotine: cell-specific receptor and circuit alterations in basal gangliaR01AG033954 · NIA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2009 to 2013
$1.7M
Role of nAChR stoichiometry in nicotine-induced upregulationF32DA030877 · NIDA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI RICHARDS, CHRISTOPHER I · 2011 to 2012
$71k
NIA NIH HHS AG-033954NIA NIH HHS R01 AG033954NIDA NIH HHS DA030877NIDA NIH HHS F32 DA030877NIDA NIH HHS R01 DA017279NINDS NIH HHS NS-11756NINDS NIH HHS NS-34407NINDS NIH HHS R01 NS011756NINDS NIH HHS R01 NS034407NINDS NIH HHS R37 NS034407
6 · The paper itself

Abstract

We provide a theory for employing Förster resonance energy transfer (FRET) measurements to determine altered heteropentameric ion channel stoichiometries in intracellular compartments of living cells. We simulate FRET within nicotinic receptors (nAChRs) whose α4 and β2 subunits contain acceptor and donor fluorescent protein moieties, respectively, within the cytoplasmic loops. We predict FRET and normalized FRET (NFRET) for the two predominant stoichiometries, (α4)(3)(β2)(2)vs. (α4)(2)(β2)(3). Studying the ratio between FRET or NFRET for the two stoichiometries, minimizes distortions due to various photophysical uncertainties. Within a range of assumptions concerning the distance between fluorophores, deviations from plane pentameric geometry, and other asymmetries, the predicted FRET and NFRET for (α4)(3)(β2)(2) exceeds that of (α4)(2)(β2)(3). The simulations account for published data on transfected Neuro2a cells in which α4β2 stoichiometries were manipulated by varying fluorescent subunit cDNA ratios: NFRET decreased monotonically from (α4)(3)(β2)(2) stoichiometry to mostly (α4)(2)(β2)(3). The simulations also account for previous macroscopic and single-channel observations that pharmacological chaperoning by nicotine and cytisine increase the (α4)(2)(β2)(3) and (α4)(3)(β2)(2) populations, respectively. We also analyze sources of variability. NFRET-based monitoring of changes in subunit stoichiometry can contribute usefully to studies on Cys-loop receptors.

Indexed as

Fluorescence Resonance Energy TransferProtein SubunitsProtein TransportReceptors, Nicotinicnicotinic receptor alpha4beta2Protein SubunitsReceptors, Nicotiniccytisineion channelsNFRETnicotinenicotine addictionParkinson’s disease

Identifiers

PMID22949846
PMCPMC3431844

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Registered trials

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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.