Browse by author
Lookup NU author(s): Emerita Professor Katherine Bushby
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Muscular dystrophies comprise a genetically heterogeneous group of degenerative muscle disorders characterized by progressive muscle wasting and weakness. Two forms of limb-girdle muscular dystrophy, 2A and 2B, are caused by mutations in calpain 3 (CAPN3) and dysferlin (DYSF), respectively. While CAPN3 may be involved in sarcomere remodeling, DYSF is proposed to play a role in membrane repair. The coexistence of CAPN3 and AHNAK, a protein involved in subsarcolemmal cytoarchitecture and membrane repair, in the dysferlin protein complex and the presence of proteolytic cleavage fragments of AHNAK in skeletal muscle led us to investigate whether AHNAK can act as substrate for CAPN3. We here demonstrate that AHNAK is cleaved by CAPN3 and show that AHNAK is lost in cells expressing active CAPN3. Conversely, AHNAK accumulates when calpain 3 is defective in skeletal muscle of calpainopathy patients. Moreover, we demonstrate that AHNAK fragments cleaved by CAPN3 have lost their affinity for dysferlin. Thus, our findings suggest interconnectivity between both diseases by revealing a novel physiological role for CAPN3 in regulating the dysferlin protein complex. © The Author 2008. Published by Oxford University Press. All rights reserved.
Author(s): Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants RR, Dunnen JT, van der Maarel SM
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2008
Volume: 17
Issue: 12
Pages: 1855-1866
Print publication date: 15/06/2008
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddn081
DOI: 10.1093/hmg/ddn081
PubMed id: 18334579
Altmetrics provided by Altmetric
