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Science 27 February 1998:
Vol. 279. no. 5355, pp. 1358 - 1360
DOI: 10.1126/science.279.5355.1358
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Reports

Melatonin Production: Proteasomal Proteolysis in Serotonin N-Acetyltransferase Regulation

Jonathan A. Gastel, Patrick H. Roseboom, Peter A. Rinaldi, Joan L. Weller, David C. Klein *

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.

Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892-4480, USA.
*   To whom correspondence should be addressed. E-mail: klein{at}helix.nih.gov

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