Talk abstracts

Talk on Wednesday 11:20-11:35am submitted by Eric Johnson

Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

Eric K. Johnson (The Ohio State Biochemistry Program, The Ohio State University), Liwen Zhang, Kari Green-Church (Center for Biomedical EPR Spectroscopy and Imaging, The Ohio State University), Marvin E Adams, Stanley C. Froehner (Department of Physiology & Biophysics, University of Washington), Alistair Phillips (Division of Cardiothoracic Surgery, The Heart Institute, Cincinnati Childrens Hospital), Michael A Freitas (Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University ), Federica Montanaro (Department of Pediatrics, The Ohio State University College of Medicine)

Abstract:
Dystrophin is a large cytoskeletal protein expressed in both skeletal and cardiac muscle. It is the central organizer of a large protein complex that performs cell signaling and structural functions. Mutations in dystrophin result in muscular dystrophy and cardiomyopathy leading to early mortality due to respiratory or heart failure. However, there is no correlation in the age of onset or severity of disease between skeletal and cardiac muscles. This suggests muscle-specific differences in dystrophin interactions and therefore functions whose identification is highly relevant to our understanding of mechanisms underlying heart failure and to the development of effective cardiac treatments.

Here, we report the successful combination of a high throughput proteomics approach incorporating immunoprecipitation of dystrophin with shotgun proteomics to rapidly and reliably identify dystrophin interacting proteins in cardiac and skeletal muscles. This approach revealed that the interactome of dystrophin in cardiac and skeletal muscle differ. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to be involved in cardiac disease.

Overall, our results suggest that dystrophin is part of a cardiac network of proteins that regulates ion channel activity, the beta-adrenergic response and structural integrity of the sarcomere. Our findings provide for the first time a molecular basis for the reported discrepancies in clinical presentation and response to treatment between cardiac and skeletal muscle in muscular dystrophy.

Keywords: Proteomics, Cardiomyopathy, Immunoprecipitation