Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Titin, the biggest single (poly) peptide found in humans, and throughout nature so far, was long considered as a good candidate for inherited muscle diseases. However, disease-causing defects were not known until recently, when this central sarcomeric protein was associated with human skeletal tibial muscular dystrophy (TMD/LGMD2J), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Several mutations in different parts of titin have now been identified and more are expected. Spontaneous mouse and zebrafish mutants have also been reported. Experimental knock-outs are not viable, even in cases where just a c-terminal part of the gene was silenced, telling something of the basic importance of titin for life. In this article we review the current known structure and functions of this elementary molecule with some emphasis on the only defects so far known to cause human skeletal muscle disease, mutations in the c-terminal M-line part of titin.
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PMID:The role of titin in muscular disorders. 1457 68

Mutations in the C terminus of titin, situated at the M-band of the striated muscle sarcomere, cause tibial muscular dystrophy (TMD) and limb-girdle muscular dystrophy (LGMD) type 2J. Mutations in the protease calpain 3 (CAPN3), in turn, lead to LGMD2A, and secondary CAPN3 deficiency in LGMD2J suggests that the pathomechanisms of the diseases are linked. Yeast two-hybrid screens carried out to elucidate the molecular pathways of TMD/LGMD2J and LGMD2A resulted in the identification of myospryn (CMYA5, cardiomyopathy-associated 5) as a binding partner for both M-band titin and CAPN3. Additional yeast two-hybrid and coimmunoprecipitation studies confirmed both interactions. The interaction of myospryn and M-band titin was supported by localization of endogenous and transfected myospryn at the M-band level. Coexpression studies showed that myospryn is a proteolytic substrate for CAPN3 and suggested that myospryn may protect CAPN3 from autolysis. Myospryn is a muscle-specific protein of the tripartite motif superfamily, reported to function in vesicular trafficking and protein kinase A signaling and implicated in the pathogenesis of Duchenne muscular dystrophy. The novel interactions indicate a role for myospryn in the sarcomeric M-band and may be relevant for the molecular pathomechanisms of TMD/LGMD2J and LGMD2A.
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PMID:Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies. 2063 90