Evolution and cell biology of dopamine receptors in vertebrates

Abstract

Dopamine, one of main modulatory neurotransmitters of the nervous system acts on target cells through two classes of G protein-coupled receptors, D 1 and D 2 . The two dopamine receptor classes display different structures, interact with different regulatory partners (including heterotrimeric G proteins) and, accordingly, have independent evolutionary origins. In vertebrates, each of these receptor classes comprises several subtypes, generated by two steps of gene duplications, early in vertebrate evolution. In the D 1 receptor class, the D 1A , D 1B , D 1C and D 1D subtypes, and in the D 2 class, the D 2 , D 3 et D 4 receptor subtypes have been conserved in most vertebrate groups. This conservation has been driven by the acquisition, by each receptor subtype, of a small number of specific properties, which were selected for adaptive purpose in vertebrates. Among these properties, affinity for dopamine, the natural ligand, intrinsic receptor activity, and agonist-induced desensitization clearly distinguish the receptor subtypes. In addition, each dopamine receptor subtype is addressed to a specific location within neuronal networks, although detailed information is lacking for several receptor subtypes. Receptors localization at diverse subcellular places in neurons may also differ from one subtype to another, resulting in different ways of regulating cell signalisation. One challenge for future research on dopamine and its receptors would be to identify the nature of the protein partners and the molecular mechanisms involved in localizing receptors to the neuronal plasma membrane. In this respect, the evolutionary approach we have undertaken suggests that, due to gene duplications, a reasonable degree of freedom exists in the tight organisation of dopamine receptors in neurons. This "evolvability" of dopamine systems has been instrumental to adapt the vertebrate species to nearly all the possible environments.

Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice

“…Comparing between the two subtypes, the D2R exhibits higher expression in dorsal striatum, substantia nigra, and ventral tegmental area, whereas the D3R exhibits higher expression in nucleus accumbens (Callier et al, 2003). Also, differential pre-vs postsynaptic expression of the receptor subtypes in brain regions important for PPI may contribute to different effects on PPI.…”

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

“…The Rhodopsin-like family expanded substantially in Metazoa, and the specific diversification of biogenic amine receptors has contributed significantly to central nervous system functioning (Callier et al, 2003;Nichols and Nichols, 2008). Like all GPCRs, biogenic amine receptors have a charcterisitic, highly-conserved structure of seven transmembrane (TM) domains separated by three extracellular (ECL) and three intracellular (ICL) loops, and they propagate intracellular signaling through a G protein-mediated pathway.…”

“…In spite of these receptors' biological and clinical importance, studies on their evolution are limited and have predomi-nantly focused on individual receptor subtypes, namely TAAR (Gloriam et al, 2005;Lindemann et al, 2005;Hashiguchi and Nishida, 2007), DRD (Callier et al, 2003;Yamamoto et al, 2013), and 5HTR (Anbazhagan et al, 2010). Moreover, many of these studies, and indeed studies on the general evolution of the Rhodopsin-like family, have examined very narrow species distributions, for instance specifically teleosts (Gloriam et al, 2005), primates (Anbazhagan et al, 2010), humans and mice (Vassilatis et al, 2003;Kakarala and Jamil, 2014), or even strictly humans (Fredriksson et al, 2003).…”

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

“…The action of DA occurs by binding to postsynaptic DA receptors, resulting in the formation of second messengers. There are fi ve subtypes of DA receptors, which can be grouped into two classes or families: D1-like and D-2 like [1,2] . The D1-like receptor family comprises the D1 and D5 receptors, encoded by genes with no introns, acting by way of Gs-proteins and activating adenylyl cyclase, thus increasing cAMP production [3,4] .…”