Abstract 307: Phospholipase Cε Is Involved in Gq-Dependent Protein Kinase D Activation in Cardiac Myocytes

We previously demonstrated that PLCε is a critical mediator of endothelin-1 (ET-1)- and norepinephrine (NE)-dependent hypertrophy in neonatal rat ventricular myocytes (NRVMs). Both α-adrenergic and ET-1 receptors couple to Gq as well as other G proteins. To determine if PLCε is required for Gαq-dependent hypertrophy NRVMs were infected with adenoviruses expressing wtGαq and PLCε siRNA followed by measurement of hypertrophy. PLCε-siRNA significantly inhibited Gαq-induced increases in myocyte area and atrial natriuretic factor (ANF) mRNA expression. Similarly, disruption of PLCε association with perinuclear mAKAP inhibited Gαq-dependent hypertrophy. These data suggest that ET-1 and PE signal, at least in part, through Gαq and PLCε. To explore the functional role of PLCε in ET-1/Gq dependent hypertrophy, activation of protein kinase D (PKD) in NRVMs was assessed in response to ET-1. PLCε-siRNA significantly inhibited ET-1 induced PKD activation (∼50% inhibition). Disruption of PLCε-mAKAP interactions also significantly inhibited ET-1 induced PKD activation (∼50% inhibition). We propose that PLCε scaffolded to mAKAP at the nuclear envelope responds to Gαq-dependent, as well as other hypertrophic signals, to locally regulate PKD in a process that is critical for hypertrophy development.