The extreme C-terminal region of phospholipase Cβ1 determines subcellular localization and function; the “b” splice variant mediates α1-adrenergic receptor responses in cardiomyocytes

摘要: Phospholipase Cbeta1 (PLCbeta1) exists as two splice variants, PLCbeta1a (150 kDa) and PLCbeta1b (140 kDa), which differ only in their C-terminal sequences of 64 31 amino acids, respectively. The 3 acid residues comprise a PDZ-interacting domain, whereas the sequence has no domain but contains unique proline-rich 5 from C terminus. is localized cytoplasm, targets to sarcolemma enriched caveolae. Deletion acids terminus did not alter its sarcolemmal localization, deletion entire caused cytosolic localization. A myristoylated 10 peptide selectively dissociated N-terminally GFP-tagged inhibited PLC responses alpha(1)-adrenergic agonists, with half maximal effective concentration 12 +/- 1.6 microM (mean+/-SE, n=3). similar was without effect at concentrations below 100 microM. Thus, extreme PLCbeta1 variants determine localization and, thus, function. In cardiomyocytes, initiated by receptor activation involve PLCbeta1b, selective targeting this variant provides potential therapeutic target reduce hypertrophy, apoptosis, arrhythmias.