Evidence map›Paper›PMID 32848200›Full record

ArticleCell research2021

Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium.

Elsayed Metwally, Guoli Zhao, Qifu Wang, Yong Q Zhang

Open access · greenAbstract read
In one paragraph

Article in Cell research, 2021. 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
1.8field-weighted citation impact, top 16% 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, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Comparative Gut Proteome ofMicroorganisms · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Store-operated CaExperimental biology and medicine (Maywood, N.J.) · 2023
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Enhanced Orai1-mediated store-operated CaThe Journal of biological chemistry · 2022
    Article
  13. Article
  14. 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

4 authors at 3 institutions in 3 countries.

Elsayed Metwally *State Key Laboratory for Molecular and Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.ORCID http://orcid.org/0000-0002-7471-3148
Guoli Zhao *State Key Laboratory for Molecular and Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.ORCID http://orcid.org/0000-0002-7807-5980
Qifu WangState Key Laboratory for Molecular and Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
Yong Q ZhangState Key Laboratory for Molecular and Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China. yqzhang@genetics.ac.cn.ORCID http://orcid.org/0000-0003-0581-4882
Chinese Academy of Sciences · CNBoston Children's Hospital · USSuez Canal University · EG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Calcium-dependent proteolytic calpains are implicated in a variety of physiological processes, as well as pathologies associated with calcium overload. However, the mechanism by which calpain is activated remains elusive since intracellular calcium levels under physiological conditions do not reach the high concentration range required to trigger calpain activation. From a candidate screening using the abundance of the calpain target glutamate receptor GluRIIA at the Drosophila neuromuscular junction as a readout, we uncovered that calpain activity was inhibited upon knockdown of Ttm50, a subunit of the Tim23 complex known to be involved in the import of proteins across the mitochondrial inner membrane. Unexpectedly, Ttm50 and calpain are co-localized at calcium stores Golgi and endoplasmic reticulum (ER), and Ttm50 interacts with calpain via its C-terminal domain. This interaction is required for calpain localization at Golgi/ER, and increases calcium sensitivity of calpain by roughly an order of magnitude. Our findings reveal the regulation of calpain activation by Ttm50, and shed new light on calpain-associated pathologies.

Indexed as

AnimalsCalciumCalpainDown-RegulationDrosophilaDrosophila ProteinsEndoplasmic ReticulumGolgi ApparatusHEK293 CellsHumansMitochondrial ProteinsProtein BindingReceptors, Ionotropic GlutamateRNA InterferenceRNA, Small InterferingCalciumCalpainDrosophila Proteinsglutamate receptor IIA, DrosophilaMitochondrial ProteinsReceptors, Ionotropic GlutamateRNA, Small InterferingTtm50 protein, Drosophila

Identifiers

PMID32848200
PMCPMC8115179
OpenAlexW3081270515

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.