Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A).

Department of Neurology and Pediatrics and UCLA Duchenne Muscular Dystrophy Research Center, University of California, Los Angeles, Neuroscience Research Building, 635 Young Dr. South, Los Angeles, CA 90095-7334, USA.

Limb girdle muscular dystrophy type 2A results from mutations in the gene encoding the calpain 3 protease. Mutations in this disease are inherited in an autosomal recessive fashion and result in progressive proximal skeletal muscle wasting but no cardiac abnormalities. Calpain 3 has been shown to proteolytically cleave a wide variety of cytoskeletal and myofibrillar proteins and to act upstream of the ubiquitin-proteasome pathway. In this review, we summarize the known biochemical and physiological features of calpain 3 and hypothesize why mutations result in disease.

PMID: 16934440 [PubMed - indexed for MEDLINE]