Evolutionarily conserved palmitoylation-dependent regulation of ionotropic glutamate receptors in vertebrates

Abstract

In the vertebrate central nervous system, glutamate is the major excitatory neurotransmitter. Ionotoropic glutamate receptors (iGluRs) are responsible for the glutamate-mediated postsynaptic excitation of neurons. Regulation of glutamatergic synapses in vertebrate central nervous system is critical for higher brain functions such as neural communication, memory formation, learning, emotion and behavior. Previous studies showed that post-translational protein palmitoylation, the only reversible covalent attachment of lipid to protein, regulates synaptic expression, intracellular localization and membrane trafficking of iGluRs in mammalian neurons. Here, I further focus on conservation of palmitoylation sites found in iGluR vertebrate orthologs. Analysis of databases shows that every palmitoylation sites of iGluRs have been completely conserved during evolution in the vertebrate lineage, in spite of the divergence of iGluRs amino acid sequences. Namely, palmitoylated cysteine residues of AMPA receptors, NMDA receptors and KA receptors, are evolutionarily conserved against mutation pressure throughout vertebrate species without exception. This finding suggests that the dynamic regulation of glutamatergic synapses made possible by this reversible palmitoylation of iGluRs is critical for the vertebrate-specific refined functions of complex nervous systems.