Evidence map›Paper›PMID 25143396›Full record

ArticleMolecular biology of the cell2014

Calpain cleavage within dysferlin exon 40a releases a synaptotagmin-like module for membrane repair.

G M I Redpath, N Woolger, A K Piper, F A Lemckert, A Lek, P A Greer, K N North, S T Cooper

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

54 citing papers in PubMed, 97 citations in OpenAlex.

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  16. Article
  17. Otoferlin as a multirole CaFrontiers in cellular neuroscience · 2023
    Review
  18. Article
  19. Article
  20. Annexins and Membrane Repair Dysfunctions in Muscular Dystrophies.International journal of molecular sciences · 2021
    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

8 authors at 3 institutions in 2 countries.

G M I RedpathInstitute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, NSW 2145, Australia Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
N WoolgerInstitute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, NSW 2145, Australia Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
A K PiperInstitute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, NSW 2145, Australia Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
F A LemckertInstitute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, NSW 2145, Australia Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
A LekInstitute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, NSW 2145, Australia Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
P A GreerDepartment of Pathology and Molecular Medicine, Queen's University, Division of Cancer Biology and Genetics, Queen's Cancer Research Institute, Kingston, ON K7L 3N6, Canada.
K N NorthMurdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia, and Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, VIC 3010, Australia.
S T CooperInstitute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, NSW 2145, Australia Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia sandra.cooper@sydney.edu.au.
The University of Sydney · AUQueen's University · CARoyal Children's Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysferlin and calpain are important mediators of the emergency response to repair plasma membrane injury. Our previous research revealed that membrane injury induces cleavage of dysferlin to release a synaptotagmin-like C-terminal module we termed mini-dysferlinC72. Here we show that injury-activated cleavage of dysferlin is mediated by the ubiquitous calpains via a cleavage motif encoded by alternately spliced exon 40a. An exon 40a-specific antibody recognizing cleaved mini-dysferlinC72 intensely labels the circumference of injury sites, supporting a key role for dysferlinExon40a isoforms in membrane repair and consistent with our evidence suggesting that the calpain-cleaved C-terminal module is the form specifically recruited to injury sites. Calpain cleavage of dysferlin is a ubiquitous response to membrane injury in multiple cell lineages and occurs independently of the membrane repair protein MG53. Our study links calpain and dysferlin in the calcium-activated vesicle fusion of membrane repair, placing calpains as upstream mediators of a membrane repair cascade that elicits cleaved dysferlin as an effector. Of importance, we reveal that myoferlin and otoferlin are also cleaved enzymatically to release similar C-terminal modules, bearing two C2 domains and a transmembrane domain. Evolutionary preservation of this feature highlights its functional importance and suggests that this highly conserved C-terminal region of ferlins represents a functionally specialized vesicle fusion module.

Indexed as

Amino Acid SequenceAnimalsCalcium-Binding ProteinsCalpainCarrier ProteinsCell MembraneCells, CulturedDysferlinHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsMembrane FusionMembrane ProteinsMiceMice, Inbred C57BLMolecular Sequence DataCalcium-Binding ProteinsCalpainCapn2 protein, mouseCapns1 protein, mouseCarrier ProteinsDysferlinDYSF protein, humanMembrane ProteinsMuscle ProteinsMYOF protein, humanOTOF protein, humanProtein IsoformsSynaptotagminsTRIM72 protein, humanTripartite Motif Proteins

Identifiers

PMID25143396
PMCPMC4230592
OpenAlexW2132087763

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.