Evidence map›Paper›PMID 17032767›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2006

Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels.

James D Brady, Elizabeth D Rich, Jeffrey R Martens, Jeffrey W Karpen, Michael D Varnum, R Lane Brown

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

45 citing papers in PubMed, 77 citations in OpenAlex.

  1. Trial
  2. Article
  3. Heat- and PIP2-dependent TRPM4 activity underlies mutually exclusive human diseases.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Ribosomal targeting strategy and nuclear labeling to analyze photoreceptor phosphoinositide signatures.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022
    Article
  6. Article
  7. Article
  8. Differential Regulation of CaInternational journal of molecular sciences · 2021
    Article
  9. Article
  10. Review
  11. Article
  12. The Enigmatic Role of Lipids in Cilia Signaling.Frontiers in cell and developmental biology · 2020
    Review
  13. Article
  14. Article
  15. Article
  16. Phosphoinositides regulate ion channels.Biochimica et biophysica acta · 2015
    Review
  17. Article
  18. Article
  19. Article
  20. 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 at 4 institutions in 2 countries.

James D BradyNeurological Sciences Institute, Oregon Health & Science University, Portland, OR 97006, USA.
Elizabeth D Rich
Jeffrey R Martens
Jeffrey W Karpen
Michael D Varnum
R Lane Brown
Oregon Health & Science University · USWashington State University · USInstitute of Neurological Sciences · ITUniversity of Michigan–Ann Arbor · US

Funding

Molecular Mechanisms of Retinal cGMP-Activated Ion ChannelsR01EY012836 · NEI · WASHINGTON STATE UNIVERSITY · PI VARNUM, MICHAEL D. · 2000 to 2012
$3.4M
FUNCTION AND REGULATION OF ION CHANNELS IN RETINAL RODSR01EY009275 · NEI · UNIVERSITY OF COLORADO DENVER · PI KARPEN, JEFFREY W · 1991 to 2010
$3.3M
DISSECTING ROD CNG CHANNEL FUNCTION WITH PSEUDECHETOXINR01EY012837 · NEI · OREGON HEALTH AND SCIENCE UNIVERSITY · PI BROWN, RONALD LANE · 2001 to 2003
$952k
Mechanism of Cholesterol Effects on CNG Channel FunctionF31NS052103 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI BRADY, JAMES DOUGLAS · 2005 to 2006
$69k
NEI NIH HHS EY009275NEI NIH HHS EY12836NEI NIH HHS EY12837NEI NIH HHS R01 EY009275NEI NIH HHS R01 EY012836NEI NIH HHS R01 EY012837NINDS NIH HHS F31 NS052103NINDS NIH HHS NS052103
6 · The paper itself

Abstract

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) has been proposed to modulate the odorant sensitivity of olfactory sensory neurons by inhibiting activation of cyclic nucleotide-gated (CNG) channels in the cilia. When applied to the intracellular face of excised patches, PIP3 has been shown to inhibit activation of heteromeric olfactory CNG channels, composed of CNGA2, CNGA4, and CNGB1b subunits, and homomeric CNGA2 channels. In contrast, we discovered that channels formed by CNGA3 subunits from cone photoreceptors were unaffected by PIP3. Using chimeric channels and a deletion mutant, we determined that residues 61-90 within the N terminus of CNGA2 are necessary for PIP3 regulation, and a biochemical "pulldown" assay suggests that PIP3 directly binds this region. The N terminus of CNGA2 contains a previously identified calcium-calmodulin (Ca2+/CaM)-binding domain (residues 68-81) that mediates Ca2+/CaM inhibition of homomeric CNGA2 channels but is functionally silent in heteromeric channels. We discovered, however, that this region is required for PIP3 regulation of both homomeric and heteromeric channels. Furthermore, PIP3 occluded the action of Ca2+/CaM on both homomeric and heteromeric channels, in part by blocking Ca2+/CaM binding. Our results establish the importance of the CNGA2 N terminus for PIP3 inhibition of olfactory CNG channels and suggest that PIP3 inhibits channel activation by disrupting an autoexcitatory interaction between the N and C termini of adjacent subunits. By dramatically suppressing channel currents, PIP3 may generate a shift in odorant sensitivity that does not require prior channel activity.

Indexed as

AnimalsCalciumCalmodulinCattleCell LineCyclic GMPCyclic Nucleotide-Gated Cation ChannelsHumansIon ChannelsOlfactory Receptor NeuronsPatch-Clamp TechniquesPhosphatidylinositol PhosphatesProtein IsoformsProtein SubunitsRatsRecombinant Fusion ProteinsCalciumCalmodulinCyclic GMPCyclic Nucleotide-Gated Cation ChannelsIon Channelsphosphatidylinositol 3,4,5-triphosphatePhosphatidylinositol PhosphatesProtein IsoformsProtein SubunitsRecombinant Fusion Proteins

Identifiers

PMID17032767
PMCPMC1622874
OpenAlexW1998170748

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.