Evidence map›Paper›PMID 23033479›Full record

ArticleThe Journal of biological chemistry2012

Calretinin regulates Ca2+-dependent inactivation and facilitation of Ca(v)2.1 Ca2+ channels through a direct interaction with the α12.1 subunit.

Carl J Christel, Raphael Schaer, Shiyi Wang, Thomas Henzi, Lisa Kreiner, Detlev Grabs, Beat Schwaller, Amy Lee

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 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
1.7field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Cytosolic CaCold Spring Harbor perspectives in biology · 2020
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  16. Effect of T-type calcium channel blockers on spiral ganglion neurons of aged C57BL/6J mice.International journal of clinical and experimental medicine · 2015
    Article
  17. Ion channels under the sun.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014
    Article
  18. 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

8 authors at 3 institutions in 2 countries.

Carl J ChristelDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, USA.
Raphael Schaer
Shiyi Wang
Thomas Henzi
Lisa Kreiner
Detlev Grabs
Beat Schwaller
Amy Lee
University of Fribourg · CHUniversity of Iowa · USEmory University · US

Funding

Regulation of auditory calcium channelsR01DC009433 · NIDCD · UNIVERSITY OF IOWA · PI LEE, AMY · 2009 to 2018
$3.6M
Modulation of Cav 1.3 L-type Ca2+ channels by PDZ-protein interactionsR01HL087120 · NHLBI · UNIVERSITY OF IOWA · PI LEE, AMY · 2009 to 2012
$1.4M
Regulation of auditory calcium channelsR55DC009433 · NIDCD · EMORY UNIVERSITY · PI LEE, AMY · 2008 to 2008
$100k
NHLBI NIH HHS R01 HL087120NIDCD NIH HHS DC009433NIDCD NIH HHS R01 DC009433NIDCD NIH HHS R55 DC009433PHS HHS T32007121
6 · The paper itself

Abstract

Voltage-gated Ca(v)2.1 Ca(2+) channels undergo dual modulation by Ca(2+), Ca(2+)-dependent inactivation (CDI), and Ca(2+)-dependent facilitation (CDF), which can influence synaptic plasticity in the nervous system. Although the molecular determinants controlling CDI and CDF have been the focus of intense research, little is known about the factors regulating these processes in neurons. Here, we show that calretinin (CR), a Ca(2+)-binding protein highly expressed in subpopulations of neurons in the brain, inhibits CDI and enhances CDF by binding directly to α(1)2.1. Screening of a phage display library with CR as bait revealed a highly basic CR-binding domain (CRB) present in multiple copies in the cytoplasmic linker between domains II and III of α(1)2.1. In pulldown assays, CR binding to fusion proteins containing these CRBs was largely Ca(2+)-dependent. α(1)2.1 coimmunoprecipitated with CR antibodies from transfected cells and mouse cerebellum, which confirmed the existence of CR-Ca(v)2.1 complexes in vitro and in vivo. In HEK293T cells, CR significantly decreased Ca(v)2.1 CDI and increased CDF. CR binding to α(1)2.1 was required for these effects, because they were not observed upon substitution of the II-III linker of α(1)2.1 with that from the Ca(v)1.2 α(1) subunit (α(1)1.2), which lacks the CRBs. In addition, coexpression of a protein containing the CRBs blocked the modulatory action of CR, most likely by competing with CR for interactions with α(1)2.1. Our findings highlight an unexpected role for CR in directly modulating effectors such as Ca(v)2.1, which may have major consequences for Ca(2+) signaling and neuronal excitability.

Indexed as

AnimalsCalbindin 2CalciumCalcium Channels, N-TypeCalcium SignalingCerebellumHEK293 CellsHumansMiceNerve Tissue ProteinsNeuronsProtein Structure, TertiaryS100 Calcium Binding Protein GCALB2 protein, humanCalb2 protein, mouseCalbindin 2CalciumCalcium Channels, N-TypeNerve Tissue ProteinsS100 Calcium Binding Protein G

Identifiers

PMID23033479
PMCPMC3501022
OpenAlexW1963539924

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.