Evidence map›Paper›PMID 18951024›Full record

ArticleCurrent biology : CB2008

An expanded biological repertoire for Ins(3,4,5,6)P4 through its modulation of ClC-3 function.

Jennifer Mitchell, Xueqing Wang, Guangping Zhang, Martina Gentzsch, Deborah J Nelson, Stephen B Shears

Open access · bronzeAbstract read
In one paragraph

Article in Current biology : CB, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. A short history of inositol lipids.Journal of lipid research · 2016
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Regulation of inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) by reversible lysine acetylation.Proceedings of the National Academy of Sciences of the United States of America · 2012
    Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Jennifer MitchellInositol Signaling Group, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA.
Xueqing Wang
Guangping Zhang
Martina Gentzsch
Deborah J Nelson
Stephen B Shears
University of Chicago · USNational Institute of Environmental Health Sciences · USNational Institutes of Health · USUniversity of North Carolina at Chapel Hill · US

Funding

Inositol SignallingZIAES080046 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI SHEARS, STEPHEN B · 2009 to 2023
$31.3M
THE BIOLOGY OF MUCUS AND MUCUS PLAQUES ON CF AIRWAYSP50HL060280 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHUA, MICHAEL · 1998 to 2007
$14.0M
REGULATION OF INOSITOL LIPID SIGNALLING MECHANISMSZ01ES080046 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI SHEARS, STEPHEN B · 1990 to 2008
$4.3M
ROLE OF ION CHANNELS IN MONONUCLEAR PHAGOCYTE ACTIVATIONR01GM036823 · NIGMS · UNIVERSITY OF CHICAGO · PI NELSON, DEBORAH J. · 1986 to 2012
$3.2M
Chloride Channel Involvement in DiabetesR56DK080364 · NIDDK · UNIVERSITY OF CHICAGO · PI NELSON, DEBORAH J. · 2007 to 2007
$92k
Intramural NIH HHS Z01 ES080046NHLBI NIH HHS P50 HL060280NHLBI NIH HHS P50 HL60280NIDDK NIH HHS R56 DK080364NIGMS NIH HHS R01 GM036823NIGMS NIH HHS R01 GM36823
6 · The paper itself

Abstract

Ins(3,4,5,6)P(4) inhibits plasma membrane Cl(-) flux in secretory epithelia [1]. However, in most other mammalian cells, receptor-dependent elevation of Ins(3,4,5,6)P(4) levels is an "orphan" response that lacks biological significance [2]. We set out to identify Cl(-) channel(s) and/or transporter(s) that are regulated by Ins(3,4,5,6)P4 in vivo. Several candidates [3-5] were excluded through biophysical criteria, electrophysiological analysis, and confocal immunofluorescence microscopy. Then, we heterologously expressed ClC-3 in the plasma membrane of HEK293-tsA201 cells; whole-cell patch-clamp analysis showed Ins(3,4,5,6)P4 to inhibit Cl(-) conductance through ClC-3. Next, we heterologously expressed ClC-3 in the early endosomal compartment of BHK cells; by fluorescence ratio imaging of endocytosed FITC-transferrin, we recorded intra-endosomal pH, an in situ biosensor for Cl(-) flux across endosomal membranes [6]. A cell-permeant, bioactivatable Ins(3,4,5,6)P4 analog elevated endosomal pH from 6.1 to 6.6, reflecting inhibition of ClC-3. Finally, Ins(3,4,5,6)P(4) inhibited endogenous ClC-3 conductance in postsynaptic membranes of neonatal hippocampal neurones. Among other ClC-3 functions that could be regulated by Ins(3,4,5,6)P4 are tumor cell migration [7], apoptosis [8], and inflammatory responses [9]. Ins(3,4,5,6)P4 is a ubiquitous cellular signal with diverse biological actions.

Indexed as

Signal TransductionAnimalsCaco-2 CellsCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell MembraneChloride ChannelsCricetinaeElectrophysiologyEndosomesHumansHydrogen-Ion ConcentrationInositol PhosphatesMembrane PotentialsNeuronsPatch-Clamp TechniquesRatsCalcium-Calmodulin-Dependent Protein Kinase Type 2Chloride Channelsinositol-3,4,5,6-tetrakisphosphateInositol Phosphates

Identifiers

PMID18951024
PMCPMC2631652
OpenAlexW1980008517

What OpenQuestion holds

Textmetadata
LicenceTDM
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.