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Functional and Structural Analysis of the Cardiac Proteins Associated to the Z Disc, Calsarcin and Enigma

Grant number: 11/01356-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2011
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Kleber Gomes Franchini
Grantee:Carlos Roberto Koscky Paier
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil
Associated research grant:06/54878-3 - Pathogenesis of cardiac hypertrophy and failure: mechanisms activated by mechanical stress, AP.TEM

Abstract

Recently, were identified sarcomeric proteins interactions with signalling partners that are able to move among subcellular compartments of cardiomyocites. It was also observed that the cardiac fibers are sensitive to mechanical stress, which respond through activation of signaling pathways (a phenomenon called "mechano-signalling" or "signal mechanotransduction"). It is believed that this process is implicated in cardiac hypertrophy. In this context, the large number of signaling proteins associated with components of the Z-line revealed an emerging role of this structure in mechanotransduction in striated muscles. Among these proteins are Calsarcin (Myozenin) and Enigma (PDLIM7). This project aims the structural resolution of these targets and/or of their recombinant protein complexes through structural biology techniques. It is also proposed the search for new interaction partners of these proteins, performed through pull-down experiments with protein extract of stretched and non-stretched cardiomyocytes. Once solved the issues regarding the structure of the proteins, it is expected to evaluate their functions through cell culture models and genetically modified mice.