Seminar Friday 12.02 at 11:00
Andres Maturana talks abouit scaffold proteins, splice variants and signaling
Title of his talk: Splice variants of the scaffold protein Enigma Homolog, differentially promote or prevent cardiac hypertrophy.
Time and place: Friday 12. February at 11.00 in seminar room 2, New Research Building, Institute for Cancer Research, Montebello.
Andres is working on cardiac hypertrophy and mainly uses rat model.
He has kindly accepted to combine a private visit with a scientific seminar.
His talk is of general interest for two reasons:
1) Scaffold proteins are most probably the main players in signal transduction specificity.
2) Here, the same gene produces two splice variants with opposite effects.
If you wish to discuss with Andres before or after his talk, just contact Sébastien Patzke 2278 1317).
Splice variants of the scaffold protein Enigma Homolog, differentially promote or prevent cardiac hypertrophy.
Proteins with a PDZ and one to three LIM domains (PDZ-LIM proteins) are scaffolding sarcomeric and cytoskeletal elements to form structured muscle fibers and provide for the link to intracellular signaling by selectively associating protein kinases, ion channels and transcription factors with the mechanical stress-strain sensors. More than 10 genes encode PDZ-LIM proteins which are further diversified by alternative splicing. Enigma homolog (ENH) is a PDZ-LIM protein with four splice variants: ENH1 with a N-terminal PDZ domain and three C-terminal LIM domains, and ENH2, ENH3 and ENH4 without LIM domains. ENH1 was first discovered as a PKCb interacting partner but its biological function was so far poorly understood. Recently, we identified two new binding partners for ENH1 in cardiomyocytes, namely protein kinase D1, which plays a critical role in the cardiovascular system and a1C, the pore sub-unit of the L-type calcium channel. Thus ENH1 connects a major signaling pathway with calcium entry required to sustain contractile activity. To address the functional role of alternative splicing of ENH, we have studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3 and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy producing an ENH isoform pattern similar to neonatal heart. As this change occurred early, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When over-expressed in neonatal cardiomyocytes, ENH1 was found to promote the expression of hypertrophy markers and increase cell size, whereas, on the contrary, over-expression of ENH4 prevented these changes. Thus, antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signaling occurring during embryonic development and/or heart hypertrophy.