Posttranslational regulation of TPH1 is responsible for the nightly surge of 5-HT output in the rat pineal gland.
Posttranslational regulation of TPH1 is responsible for the nightly surge of 5-HT output in the rat pineal gland.
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DOI：
10.1111/j.1600-079x.2008.00627.x
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发表时间：
2008-11
影响因子：
10.3
通讯作者：
Borjigin J
中科院分区：
文献类型：
--
作者：
Huang Z;Liu T;Chattoraj A;Ahmed S;Wang MM;Deng J;Sun X;Borjigin J
5-羟色胺（5-hydroxytryptamine，5-HT）是褪黑激素的前体，在所有脊椎动物的松果体中大量产生。松果体中5-HT的合成受色氨酸羟化酶1（TPH 1）的限制，其活性在夜间增加两倍。我们实验室的早期研究表明，松果体5-HT分泌具有动态的昼夜节律，在夜间水平升高，并且这种增加是由夜间肾上腺素能信号控制的。在这项研究中，我们报告（a）5-HT总输出量和TPH 1蛋白水平都显示昼夜节律，在夜间增加两倍;（B）cAMP信号刺激提高5-HT输出在体内;（c）5-HT总输出量和TPH 1蛋白含量在大鼠松果体都急性抑制光照在夜间。与这些发现一致，TPH 1蛋白的分子分析揭示：（a）体外和夜间松果体中TPH 1在丝氨酸58处磷酸化;和（B）cAMP增强的TPH 1蛋白稳定性需要TPH 1在该残基处的磷酸化。这些数据支持了松果体夜间5-HT合成增加是由TPH 1在丝氨酸58处磷酸化介导的模型，这提高了TPH 1蛋白的含量和活性。
Serotonin (5-hydroxytryptamine, 5-HT), a precursor for melatonin production, is produced abundantly in the pineal gland of all vertebrate animals. The synthesis of 5-HT in the pineal gland is rate limited by tryptophan hydroxylase 1 (TPH1) whose activity displays a twofold increase at night. Earlier studies from our laboratory demonstrate that pineal 5-HT secretion exhibits dynamic circadian rhythms with elevated levels during the early night, and that the increase is controlled by adrenergic signaling at night. In this study, we report that (a) 5-HT total output from the pineal gland and TPH1 protein levels both display diurnal rhythms with a twofold increase at night; (b) stimulation of cAMP signaling elevates 5-HT output in vivo; (c) 5-HT total output and TPH1 protein content in rat pineal gland are both acutely inhibited by light exposure at night. Consistent with these findings, molecular analysis of TPH1 protein revealed that (a) TPH1 is phosphorylated at the serine 58 in vitro and in the night pineal gland; and (b) phosphorylation of TPH1 at this residue is required for cAMP-enhanced TPH1 protein stability. These data support the model that increased nocturnal 5-HT synthesis in the pineal gland is mediated by the phosphorylation of TPH1 at the serine 58, which elevates the TPH1 protein content and activity at night.