Evidence map›Paper›PMID 19923421›Full record

ArticleAmerican journal of physiology. Cell physiology2010

Phosphatidylinositol 4,5-bisphosphate and loss of PLCgamma activity inhibit TRPM channels required for oscillatory Ca2+ signaling.

Juan Xing, Kevin Strange

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Cell physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

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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

2 authors at 2 institutions in 1 country.

Juan XingDepartment of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Kevin Strange
Mount Desert Island Biological Laboratory · USVanderbilt University Medical Center · US

Funding

Oscillatory Ca2+ signaling in the C.elegans intestineR01GM074229 · NIGMS · VANDERBILT UNIVERSITY · PI STRANGE, KEVIN · 2006 to 2009
$1.1M
NIGMS NIH HHS GM-74229
6 · The paper itself

Abstract

The Caenorhabditis elegans intestinal epithelium generates rhythmic inositol 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) oscillations that control muscle contractions required for defecation. Two highly Ca(2+)-selective transient receptor potential (TRP) melastatin (TRPM) channels, GON-2 and GTL-1, function with PLCgamma in a common signaling pathway that regulates IP(3)-dependent intracellular Ca(2+) release. A second PLC, PLCbeta, is also required for IP(3)-dependent Ca(2+) oscillations, but functions in an independent signaling mechanism. PLCgamma generates IP(3) that regulates IP(3) receptor activity. We demonstrate here that PLCgamma via hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP(2)) also regulates GON-2/GTL-1 function. Knockdown of PLCgamma but not PLCbeta activity by RNA interference (RNAi) inhibits channel activity approximately 80%. Inhibition is fully reversed by agents that deplete PIP(2) levels. PIP(2) added to the patch pipette has no effect on channel activity in PLCgamma RNAi cells. However, in control cells, 10 microM PIP(2) inhibits whole cell current approximately 80%. Channel inhibition by phospholipids is selective for PIP(2) with an IC(50) value of 2.6 microM. Elevated PIP(2) levels have no effect on channel voltage and Ca(2+) sensitivity and likely inhibit by reducing channel open probability, single-channel conductance, and/or trafficking. We conclude that hydrolysis of PIP(2) by PLCgamma functions in the activation of both the IP(3) receptor and GON-2/GTL-1 channels. GON-2/GTL-1 functions as the major intestinal cell Ca(2+) influx pathway. Calcium influx through the channel feedback regulates its activity and likely functions to modulate IP(3) receptor function. PIP(2)-dependent regulation of GON-2/GTL-1 may provide a mechanism to coordinate plasma membrane Ca(2+) influx with PLCgamma and IP(3) receptor activity as well as intracellular Ca(2+) store depletion.

Indexed as

Calcium SignalingAnimalsBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsFeedback, PhysiologicalGATA Transcription FactorsHydrolysisInositol 1,4,5-Trisphosphate ReceptorsIntestinal MucosaIon Channel GatingIon ChannelsKineticsMembrane PotentialsPeriodicityPhosphatidylinositol 4,5-DiphosphateCaenorhabditis elegans ProteinsEgl-8 protein, C elegansELT-1 protein, C elegansGATA Transcription FactorsGON-2 protein, C elegansGTL-1 protein, C elegansInositol 1,4,5-Trisphosphate ReceptorsIon ChannelsPhosphatidylinositol 4,5-DiphosphatePhospholipase C betaPhospholipase C gammaPhospholipidsRecombinant Fusion Proteins

Identifiers

PMID19923421
PMCPMC2822497
OpenAlexW2154900804

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.