PROTEIN MODIFICATIONS IN VENTRICULAR SPECIFIC erbB4-

Montevideo

Otro; EMBO World Practical Course: Mass Spectrometry in Protein Analysis and Characterization.; 2010

EMBO y Instituto Pasteur de Montevideo

Neuregulin-1 signaling through tyrosine kinase receptors erbB2 and erbB4 is critical for the maintenance of adult heart structure and function. To understand the activities of neuregulin signaling in the heart, our laboratory generated a ventricular specific erbB4-knockout mouse (erbB4-KO). This conditional mutant leads to adult ventricular dilation with a 60% reduction in contractility. Both erbB2 and erbB4 protein accumulate in the T-tubules. This location may functionally relate these receptors to cytoskeletal pathways that modulate myofibrillar organization or function. The depressed myocardial contractility occurs without apparent changes in calcium transients or cytosolic concentration in individual cardiomyocytes. Therefore, we investigated potential modifications of the properties of myofibril components that could be underlying the impaired ability of the myocardium to transmit or generate force. Towards this aim, we analyzed ventricular protein extracts by bidimensional electrophoresis (2D-PAGE), protein phosphorylation and further mass spectrometry on peptide digest to identify modified proteins in the KO compared to Wt. In this regard, the identification of molecular targets may help understanding the requirement of the erbB2/erB4 in the heart.