Comparative analysis of palmitoylation sites of serotonin (5-HT) receptors in vertebrates.
Comparative analysis of palmitoylation sites of serotonin (5-HT) receptors in vertebrates.
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DOI：
10.1002/npr2.12011
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发表时间：
2018-06
影响因子：
2.5
通讯作者：
Hayashi T
中科院分区：
文献类型：
--
作者：
Kaizuka T;Hayashi T
在脊椎动物中枢神经系统以及外周中，5-羟色胺，也称为5-羟基曲丁胺（5-HT），作为神经递质，激素或有丝分裂原发挥作用。5-HT受体由7个5-HT 1 - 7受体家族组成，包括14种结构上不同的5-HT受体亚型。先前的实验研究表明，小鼠5-HT 1A、5-HT 4和5-HT 7受体受翻译后蛋白棕榈酰化（脂质棕榈酸酯与细胞内半胱氨酸残基的可逆连接）的调节。在这里，我们进一步关注在脊椎动物5-HT受体直系同源物中发现的这些推定的棕榈酰化位点的保守性。序列数据库的分析提供的证据表明，尽管5-HT 1A，5-HT 4或5-HT 7受体全长氨基酸序列在分子进化过程中存在差异，但这些5-HT受体的棕榈酰化位点在从无颌鱼类到人类的脊椎动物谱系中非常保守。我们的研究结果意味着通过可逆的翻译后蛋白棕榈酰化实现的5-HT受体的动态调节可能对脊椎动物多巴胺能系统的精细功能至关重要。5-HT 1A、5-HT 4和5-HT 7受体的可逆翻译后蛋白棕榈酰化位点在脊椎动物谱系中对突变压力非常保守。
In the vertebrate central nervous system as well as in the periphery, serotonin, also known as 5‐hydroxytriptamine (5‐HT), function as a neurotransmitter, a hormone or a mitogen. 5‐HT receptors are composed of 7 family 5‐HT 1‐7 receptors, comprising of 14 structurally and pharmacologically distinct 5‐HT receptor subtypes. Previous experimental studies showed that mouse 5‐HT 1A, 5‐HT 4 and 5‐HT 7 receptors are regulated by post‐translational protein palmitoylation, the reversible attachment of the lipid palmitate to intracellular cysteine residues. Here, we further focused on conservation of these putative palmitoylation sites found in vertebrate 5‐HT receptor orthologs. Analysis of sequence databases provides evidence to suggest that palmitoylation sites of these 5‐HT receptors have been extremely conserved in the vertebrate lineages from jawless fishes to human, in spite of the divergence of 5‐HT 1A, 5‐HT 4 or 5‐HT 7 receptors full‐length amino acid sequences during molecular evolution. Our findings mean that dynamic regulation of 5‐HT receptors made possible by reversible post‐translational protein palmitoylation may be critical for refined functions of the vertebrate serotonergic systems. Reversible post‐translational protein palmitoylation sites of 5‐HT1A, 5‐HT4, and 5‐HT7 receptors have been extremely conserved in the vertebrate lineages against mutation pressure.
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