Calpains, Cleaved Mini-Dysferlin(C72), and L-Type Channels Underpin Calcium-Dependent Muscle Membrane Repair

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Show simple item record Lek, A. en_US Evesson, F. en_US Lemckert, F. en_US Redpath, G. en_US North, K. en_US Cooper, S. en_US Turnbull, Lynne en_US Whitchurch, Cynthia en_US
dc.contributor.editor en_US 2013-11-03T17:05:24Z 2013-11-03T17:05:24Z 2013 en_US
dc.identifier 2012001849 en_US
dc.identifier.citation Lek, A. et al. 2013, 'Calpains, Cleaved Mini-Dysferlin(C72), and L-Type Channels Underpin Calcium-Dependent Muscle Membrane Repair', Society for Neuroscience, vol. 33, no. 12, pp. 5085-5094. en_US
dc.identifier.issn 0270-6474 en_US
dc.identifier.other C1 en_US
dc.description.abstract Dysferlin is proposed as a key mediator of calcium-dependent muscle membrane repair, although its precise role has remained elusive. Dysferlin interacts with a new membrane repair protein, mitsugumin 53 (MG53), an E3 ubiquitin ligase that shows rapid recruitment to injury sites. Using a novel ballistics assay in primary human myotubes, we show it is not full-length dysferlin recruited to sites of membrane injury but an injury-specific calpain-cleavage product, mini-dysferlin(C72). Mini-dysferlin(C72)-rich vesicles are rapidly recruited to injury sites and fuse with plasma membrane compartments decorated by MG53 in a process coordinated by L-type calcium channels. Collective interplay between activated calpains, dysferlin, and L-type channels explains how muscle cells sense a membrane injury and mount a specialized response in the unique local environment of a membrane injury. Mini-dysferlin(C72) and MG53 form an intricate lattice that intensely labels exposed phospholipids of injury sites, then infiltrates and stabilizes the membrane lesion during repair. Our results extend functional parallels between ferlins and synaptotagmins. Whereas otoferlin exists as long and short splice isoforms, dysferlin is subject to enzymatic cleavage releasing a synaptotagmin-like fragment with a specialized protein-or phospholipid-binding role for muscle membrane repair. en_US
dc.language en_US
dc.publisher Society for Neuroscience en_US
dc.relation.isbasedon en_US
dc.title Calpains, Cleaved Mini-Dysferlin(C72), and L-Type Channels Underpin Calcium-Dependent Muscle Membrane Repair en_US
dc.parent Journal of Neuroscience en_US
dc.journal.volume 33 en_US
dc.journal.number 12 en_US
dc.publocation United States en_US
dc.identifier.startpage 5085 en_US
dc.identifier.endpage 5094 en_US SCI.Institute for Biotechnology of Infectious Diseases en_US
dc.conference Verified OK en_US
dc.for 060500 en_US
dc.personcode 0000091950 en_US
dc.personcode 0000091952 en_US
dc.personcode 0000091953 en_US
dc.personcode 0000091954 en_US
dc.personcode 0000091955 en_US
dc.personcode 0000091956 en_US
dc.personcode 103744 en_US
dc.personcode 103745 en_US
dc.percentage 100 en_US Microbiology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity en_US
dc.staffid 103745 en_US

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