Molecular mechanisms of regulation of melatonin synthesis in pineal gland

点击翻译按钮获取中文摘要

Pineal gland converts time signals from SCN to hormonal signals : pinealocytes synthesize melatonin as a circadyan rhythm hormone, and secrete it through blood stream. Serotonin N-acetyltransferase (SNAT) plays a sentral role for synthesis of melatonin, and thus, its activities are definitly controlled through several pathways. In the research project, we found two distinct novel regulatory mechanisms for SNAT regulation : [I] L-glutamate-mediated autonomic regulation, and [II] intramolecular regulation through cleavage of disulfide bond. The summary of each systems are as follows :[I] Overall characteristics of the L-glutamate-mediated autonomic regulatory system. We found that pinealocytes are glutamatergic. The cells store L-glutamate in synaptic-like microvesicles and secrete it through exocytosis. The released glutamate is involved in negative regulation of melatonin synthesis. We have identified and characterized various receptors and transporters involving in the processes. We have solved the molecular mechanism of L-glutamate secretion.[II] The mechanism of intramolecular regulation of SNAT. We found that SNAT showed two forms (active and inactive state) through exchange of -S-S- to -SH and HS-. We identified two systein residues incolving the processes. We found that this regulation also occurs under physiological conditions, and play a central role in SNAT regulation.