Poster abstracts

Poster number 18 submitted by Eric Johnson

Characterization of the Dystrophin Associated Protein Complex in the Heart

Eric Johnson (Pediatrics, OSU), Liwen Zhang PhD (CCIC Mass Spectrometry and Proteomics Facility , OSU), Kari Green-Church PhD (CCIC Mass Spectrometry and Proteomics Facility , OSU), Federica Montanaro PhD (Pediatrics, OSU)

Abstract:
Dystrophin is a large protein that localizes to the inner surface of the sarcolemma of skeletal and cardiac muscle tissue. It is the central organizer of a large protein complex known as the dystrophin associated protein complex (DAPC) that links the actin cytoskeleton to the extracellular matrix. This link is critical for muscle integrity and functionality, and protects muscle fibers and cardiomyocytes from the mechanical stress of muscle contraction. Mutations in the dystrophin gene result in a wide range of muscular dystrophies. While the majority of these mutations affect both skeletal and cardiac muscle to different extents, a small subset of dystrophin mutations have a pure cardiac phenotype, primarily severe dilated cardiomyopathy. This suggests that dystrophin has cardio specific functions specifically disrupted by this subset of mutations. Several additional lines of evidence including biochemical, localization, and therapeutic studies in mice support the notion that dystrophin performs a unique subset of functions in cardiac muscle compared to skeletal muscle. We hypothesize that these cardio specific functions of dystrophin are mediated by protein interactions unique to cardiac tissue. To test this hypothesis we will be using a high throughput proteomics approach utilizing immunoprecipitation of dystrophin coupled with mass spectrometry to identify proteins that directly or indirectly interact with dystrophin only in cardiac tissue. Completion of this project will identify dystrophin interacting proteins relevant to dystrophin’s cardiac functions and candidates for dystrophin associated DCM. A better understanding of the role of dystrophin in the heart can ultimately impact therapies for DCM and define protein-protein interactions that influence pathogenesis.

References:
Dystrophin, cardiomyopathy, Immunoprecipitation, Proteomics

Keywords: Dystrophin, Immunoprecipitation, Proteomics