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Melatonin production: Proteasonal proteolysis in serotonin N-acetyltransferase regulation

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 e...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1998-02, Vol.279 (5355), p.1358-1360
Main Authors: Gastel, Jonathan A, Roseboom, Patrick H, Rinaldi, Peter A, Weller, Joan L, Klein, David C
Format: Article
Language:English
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Summary: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 beta-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.
ISSN:0036-8075
1095-9203