MELATONIN PRODUCTION - PROTEASOMAL PROTEOLYSIS IN SEROTONIN N-ACETYLTRANSFERASE REGULATION

The nocturnal increase in circulating melatonin in vertebrates is regu lated bg, 10- to 100-fold increases in pineal serotonin N-acetyltransf erase (AA-NAT) activity. Changes in the amount of AA-NAT protein were shown to parallel changes in AA-NAT activity. When neural stimulation was switched off by either light exposure or L-propranalol-induced bet a-adrenergic blockade, both AA-NAT activity and protein decreased rapi dly. Effects of L-propranolol were blocked in vitro by dibutyryl adeno sine 3',5'-monophasphate (cAMP) or inhibitors of proteasomal proteolys is. This result indicates that adrenergic-cAMP regulation of AA-NAT is mediated by rapid reversible control af selective proteasomal proteol ysis. Similar proteasome-based mechanisms may function widely as selec tive molecular switches in vertebrate neural systems.