Evidence map›Paper›PMID 27489103›Full record

ArticleThe Journal of biological chemistry2016

The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination.

Karen M Page, Simon W Rothwell, Annette C Dolphin

Abstract 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 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

24 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Pin1 promotes human CaCell communication and signaling : CCS · 2024
    Article
  5. Article
  6. Article
  7. Active Zone Trafficking of CaV2/UNC-2 Channels Is Independent of β/CCB-1 and α2δ/UNC-36 Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  8. Review
  9. Review
  10. Article
  11. Inhibitory effects on L- and N-type calcium channels by a novel CaNaunyn-Schmiedeberg's archives of pharmacology · 2022
    Article
  12. The life cycle of voltage-gated CaNeuronal signaling · 2021
    Review
  13. Article
  14. Article
  15. Review
  16. Disruption of the Key CaCell reports · 2019
    Article
  17. Review
  18. The αCell reports · 2018
    Article
  19. Article
  20. Review
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

3 authors.

Karen M PageFrom the Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St., London WC1E 6BT, United Kingdom k.page@ucl.ac.uk.
Simon W RothwellFrom the Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St., London WC1E 6BT, United Kingdom.
Annette C DolphinFrom the Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St., London WC1E 6BT, United Kingdom a.dolphin@ucl.ac.uk.

Funding

Wellcome TrustWellcome Trust 098360/Z/12/Z
6 · The paper itself

Abstract

CaVβ subunits interact with the voltage-gated calcium channel CaV2.2 on a site in the intracellular loop between domains I and II (the I-II loop). This interaction influences the biophysical properties of the channel and leads to an increase in its trafficking to the plasma membrane. We have shown previously that a mutant CaV2.2 channel that is unable to bind CaVβ subunits (CaV2.2 W391A) was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598-9611). Here we show that, in the absence of CaVβ subunits, a construct consisting of the I-II loop of CaV2.2 was directly ubiquitinated and degraded by the proteasome system. Ubiquitination could be prevented by mutation of all 12 lysine residues in the I-II loop to arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop was insufficient to target it to the plasma membrane in the absence of CaVβ subunits even when proteasomal degradation was inhibited with MG132 or ubiquitination was prevented by the lysine-to-arginine mutations. In the presence of CaVβ subunit, the palmitoylated CaV2.2 I-II loop was protected from degradation, although oligoubiquitination could still occur, and was efficiently trafficked to the plasma membrane. We propose that targeting to the plasma membrane requires a conformational change in the I-II loop that is induced by binding of the CaVβ subunit.

Indexed as

ProteolysisAmino Acid SubstitutionAnimalsCalcium Channels, N-TypeCell LineCell MembraneLipoylationMutation, MissenseProteasome Endopeptidase ComplexProtein Structure, SecondaryRabbitsRatsUbiquitinationCacna1b protein, ratCalcium Channels, N-TypeProteasome Endopeptidase Complexcalcium channelconfocal microscopyprotein degradationtraffickingubiquitinubiquitylation (ubiquitination)Western blot

Identifiers

PMID27489103
PMCPMC5034038

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Registered trials

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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.