Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A).
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.
Kramerova
Irina
I
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.
Beckmann
Jacques S
JS
Spencer
Melissa J
MJ
D000818:Animals; D002154:Calpain / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D049288:Muscular Dystrophies, Limb-Girdle / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020125:Mutation, Missense
D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain