Melatonin Production: Proteasomal Proteolysis in Serotonin N -Acetyltransferase Regulation

Abstract

The nocturnal increase in circulating melatonin in vertebrates is regulated by 10- to 100-fold increases in pineal serotonin N -acetyltransferase (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 -propranolol–induced β-adrenergic blockade, both AA-NAT activity and protein decreased rapidly. Effects of l -propranolol were blocked in vitro by dibutyryl adenosine 3′,5′-monophosphate (cAMP) or inhibitors of proteasomal proteolysis. This result indicates that adrenergic-cAMP regulation of AA-NAT is mediated by rapid reversible control of selective proteasomal proteolysis. Similar proteasome-based mechanisms may function widely as selective molecular switches in vertebrate neural systems.