Evidence map›Paper›PMID 26755721›Full record

ArticleThe Journal of biological chemistry2016

Unique Regulatory Properties of Heterotetrameric Inositol 1,4,5-Trisphosphate Receptors Revealed by Studying Concatenated Receptor Constructs.

Rahul Chandrasekhar, Kamil J Alzayady, Larry E Wagner, David I Yule

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 43 citations in OpenAlex.

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  13. IPNature communications · 2019
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  14. Calcium signalling in T cells.Nature reviews. Immunology · 2019
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  15. Crosstalk between Calcium and ROS in Pathophysiological Conditions.Oxidative medicine and cellular longevity · 2019
    Review
  16. All three IPScience signaling · 2018
    Article
  17. Article
  18. Differential regulation of ion channels function by proteolysis.Biochimica et biophysica acta. Molecular cell research · 2018
    Review
  19. Article
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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 1 institution in 1 country.

Rahul ChandrasekharFrom the Department of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642.
Kamil J AlzayadyFrom the Department of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642.
Larry E WagnerFrom the Department of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642.
David I YuleFrom the Department of Pharmacology and Physiology, University of Rochester, Rochester, New York 14642 David_Yule@urmc.rochester.edu.
University of Rochester · US

Funding

[Ca2+]i and Secretory Dynamics in Parotid Acinar CellsR01DE014756 · NIDCR · UNIVERSITY OF ROCHESTER · PI David I Yule · 2002 to 2026
$9.9M
An experimental/computational approach for understanding salivary fluid secretionR01DE019245 · NIDCR · UNIVERSITY OF ROCHESTER · PI David I Yule · 2008 to 2026
$9.7M
NIDCR NIH HHS DE019245NIDCR NIH HHS R01 DE014756NIDCR NIH HHS R01DE014756NIDCR NIH HHS R01 DE019245
6 · The paper itself

Abstract

The ability of inositol 1,4,5-trisphosphate receptors (IP3R) to precisely initiate and generate a diverse variety of intracellular Ca(2+) signals is in part mediated by the differential regulation of the three subtypes (R1, R2, and R3) by key functional modulators (IP3, Ca(2+), and ATP). However, the contribution of IP3R heterotetramerization to Ca(2+) signal diversity has largely been unexplored. In this report, we provide the first definitive biochemical evidence of endogenous heterotetramer formation. Additionally, we examine the contribution of individual subtypes within defined concatenated heterotetramers to the shaping of Ca(2+) signals. Under conditions where key regulators of IP3R function are optimal for Ca(2+) release, we demonstrate that individual monomers within heteromeric IP3Rs contributed equally toward generating a distinct 'blended' sensitivity to IP3 that is likely dictated by the unique IP3 binding affinity of the heteromers. However, under suboptimal conditions where [ATP] were varied, we found that one subtype dictated the ATP regulatory properties of heteromers. We show that R2 monomers within a heterotetramer were both necessary and sufficient to dictate the ATP regulatory properties. Finally, the ATP-binding site B in R2 critical for ATP regulation was mutated and rendered non-functional to address questions relating to the stoichiometry of IP3R regulation. Two intact R2 monomers were sufficient to maintain ATP regulation in R2 homotetramers. In summary, we demonstrate that heterotetrameric IP3R do not necessarily behave as the sum of the constituent subunits, and these properties likely extend the versatility of IP3-induced Ca(2+) signaling in cells expressing multiple IP3R isoforms.

Indexed as

Calcium SignalingProtein MultimerizationAction PotentialsAdenosine TriphosphateAnimalsCalciumCell Line, TumorCell NucleusChickensInositol 1,4,5-TrisphosphateInositol 1,4,5-Trisphosphate ReceptorsPotassiumProtein BindingAdenosine TriphosphateCalciumInositol 1,4,5-TrisphosphateInositol 1,4,5-Trisphosphate ReceptorsPotassiumATP bindingcalciumcalcium channelcalcium intracellular releaseConcatemerinositol 1,4,5-trisphosphate (IP3)inositol trisphosphate receptor (InsP3R)

Identifiers

PMID26755721
PMCPMC4777821
OpenAlexW2233214262

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.