Comparative analysis of palmitoylation sites of serotonin (5‐HT) receptors in vertebrates

Abstract

Abstract Background 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‐HT1‐7 receptors, comprising of 14 structurally and pharmacologically distinct 5‐HT receptor subtypes. Previous experimental studies showed that mouse 5‐HT1A, 5‐HT4 and 5‐HT7 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. Methods and Results 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‐HT1A, 5‐HT4 or 5‐HT7 receptors full‐length amino acid sequences during molecular evolution. Conclusion 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.

Keywords

• 5‐hydroxytryptamine
• orthologs
• post‐translational protein palmitoylation
• receptor
• serotonin
• vertebrate