RT Journal Article
SR Electronic
T1 Melatonin Production: Proteasomal Proteolysis in Serotonin <em>N</em>-Acetyltransferase Regulation
JF Science
JO Science
FD American Association for the Advancement of Science
SP 1358
OP 1360
DO 10.1126/science.279.5355.1358
VO 279
IS 5355
A1 Gastel, Jonathan A.
A1 Roseboom, Patrick H.
A1 Rinaldi, Peter A.
A1 Weller, Joan L.
A1 Klein, David C.
YR 1998
UL http://science.sciencemag.org/content/279/5355/1358.abstract
AB The nocturnal increase in circulating melatonin in vertebrates is regulated by 10- to 100-fold increases in pineal serotoninN-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 ofl-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.