Cloning and characterisation of myospryn, a novel dysbindin-binding protein in muscle

Thesis

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by mutations in the gene encoding dystrophin. Loss of dystrophin leads to the disruption of the dystrophin-associated glycoprotein complex (DGC), membrane fragility and increased intracellular calcium. Disruption of the DGC has also been implicated in the development of other muscle disorders, including cardiomyopathy. The dystrobrevins are dystrophin-associated and -related proteins which are intracellular components of the DGC. α-Dystrobrevin-deficient mice develop skeletal muscle disease and cardiomyopathy without disruption of the DGC, suggesting a link between dystrobrevin and an unidentified protein complex. Previously, it has been shown that α-dystrobrevin binds to the coiled-coil containing protein dysbindin. To gain further insight into the function of α-dystrobrevin and dysbindin in skeletal muscle, a yeast two-hybrid screen was performed to identify dysbindin-interacting proteins. Dysbindin binds to a novel, 413 kDa protein, myospryn, which is expressed in cardiac and skeletal muscle. The transcript encoding myospryn encompasses genethonin-3, which is down-regulated in muscle from DMD patients, and stretch responsive protein 553, which is up-regulated in an experimental model of muscle hypertrophy. The C-terminus of myospryn is predicted to contain BBC, FN3, and SPRY domains in a configuration reminiscent of the tripartite motif protein family.

Authors: Benson, M; Benson, Matthew Arnold

• Publication date: 2005
• DOI: 10.5287/ora-pyr7rezrz
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Diseases; Muscle; Myocardium; Duchenne muscular dystrophy; Protein binding