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

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-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.

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-HT₄ or 5-HT₇ 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.