September CDB Seminar - Professor Anant B Parekh - Oxford University

Academic Host: Claudio Stern
Abstract:
NFAT is a widely expressed Ca2+-dependent transcription factor. NFAT-dependent gene expression is essential for the development and function of the nervous, immune, and cardiovascular systems and kidney, bone, and skeletal muscle. Most NFAT protein resides in the cytoplasm because of extensive phosphorylation, which masks a nuclear localization sequence. Dephosphorylation by the Ca2+-calmodulin-activated protein phosphatase calcineurin triggers NFAT migration into the nucleus. In some cell types, NFAT can be activated by Ca2+ nanodomains near open store-operated Orai1 Ca2+ channels in the plasma membrane. In this talk, I will describe how two Ca2+-dependent transcription factor isoforms, NFAT1 and NFAT4, require distinct sub-cellular InsP3 and Ca2+ signals for physiologically sustained activation. Oscillations in cytoplasmic Ca2+, long considered the physiological form of Ca2+signaling, play no role in activating either transcription factor. I will describe how gene expression can be controlled by coincident yet geographically distinct Ca2+ signals, generated by a freely diffusible InsP3 message.