Melatonin Production: Proteasomal Proteolysis in Serotonin N-Acetyltransferase Regulation

• Published in: Science (American Association for the Advancement of Science) Vol. 279; no. 5355; pp. 1358 - 1360
• Main Authors: Gastel, Jonathan A., Roseboom, Patrick H., Rinaldi, Peter A., Weller, Joan L., Klein, David C.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 27-02-1998; American Association for the Advancement of Science
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Arylamine N-Acetyltransferase - metabolism; Biological and medical sciences; Bucladesine - pharmacology; Circadian rhythms; Cyclic AMP - metabolism; Cysteine Endopeptidases - metabolism; Cysteine Proteinase Inhibitors - pharmacology; Endocrinology; Fundamental and applied biological sciences. Psychology; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Isoproterenol - pharmacology; Light; Melatonin; Melatonin - biosynthesis; Multienzyme Complexes - metabolism; Physiological aspects; Physiological regulation; Physiology; Pineal gland; Pineal Gland - cytology; Pineal Gland - drug effects; Pineal Gland - enzymology; Pineal Gland - metabolism; Propranolol - pharmacology; Proteasome Endopeptidase Complex; Rats; Receptors, Adrenergic, beta - physiology; Vertebrates; Vertebrates: endocrinology; Acyltransferases; Multicatalytic endopeptidase complex; Melatonin; Endocrine gland; Rat; Enzyme; Transferases; Rodentia; Cyclic AMP; Neuroendocrine regulation; Pineal body; Biosynthesis; β-Adrenergic receptor; Peptidases; Vertebrata; Mammalia; Enzymatic activity; Proteolysis; Hydrolases; Norepinephrine; Aralkylamine N-acetyltransferase; Pineal hormone
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.279.5355.1358

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.