Ancestry of neuronal monoamine transporters in the Metazoa

Abstract

SUMMARY Selective Na+-dependent re-uptake of biogenic monoamines at mammalian nerve synapses is accomplished by three types of solute-linked carrier family 6 (SLC6) membrane transporter with high affinity for serotonin(SERTs), dopamine (DATs) and norepinephrine (NETs). An additional SLC6 monoamine transporter (OAT), is responsible for the selective uptake of the phenolamines octopamine and tyramine by insect neurons. We have characterized a similar high-affinity phenoloamine transporter expressed in the CNS of the earthworm Lumbricus terrestris. Phylogenetic analysis of its protein sequence clusters it with both arthropod phenolamine and chordate catecholamine transporters. To clarify the relationships among metazoan monoamine transporters we identified representatives in the major branches of metazoan evolution by polymerase chain reaction (PCR)-amplifying conserved cDNA fragments from isolated nervous tissue and by analyzing available genomic data. Analysis of conserved motifs in the sequence data suggest that the presumed common ancestor of modern-day Bilateria expressed at least three functionally distinct monoamine transporters in its nervous system: a SERT currently found throughout bilaterian phyla, a DAT now restricted in distribution to protostome invertebrates and echinoderms and a third monoamine transporter (MAT), widely represented in contemporary Bilateria, that is selective for catecholamines and/or phenolamines. Chordate DATs, NETs,epinephrine transporters (ETs) and arthropod and annelid OATs all belong to the MAT clade. Contemporary invertebrate and chordate DATs belong to different SLC6 clades. Furthermore, the genes for dopamine and norepinephrine transporters of vertebrates are paralogous, apparently having arisen through duplication of an invertebrate MAT gene after the loss of an invertebrate-type DAT gene in a basal protochordate.

The locust foraging gene

“…Lastly, serotonin (5-hydroxtryptamine, 5HT) is both necessary and sufficient for locust phase transformation, with increasing levels of 5HT accompanying (and inducing) gregariousness (Anstey et al, 2009). A connection between the 5HT transporter (SERT), present in all animals from flatworm to human (Caveney et al, 2006) and cGMP/PKG signaling is also known; activation of cGMP/PKG-linked pathways increases SERT activity and rapidly alters both 5HT uptake and clearance rates (e.g., Miller and Hoffman, 1994;Zhu et al, 2004a,b). Specifically, Zhang et al (2007) reported that PKG phosphorylates human SERT (at Thr-276) and thus increases its activity.…”

Physiological Endpoints for Potential SSRI Interactions in Fish

“…34 As a monoamine transporter, 5-HTT belongs to the solute-linked carrier 6 (SLC6) family, a diverse set of Na + /Cl − -dependent neurotransmitter transporters comprising five subfamilies. 39 Three of these subfamilies, including the monoamine transporters, are thought to share a common structural motif, namely, 12 transmembrane domains with a larger extracellular loop containing potential glycosylation sites between domains 3 and 4, and several cytoplasmic phosphorylation sites 40,41 ( Figure 3). The mammalian 5-HTT has been described in the central and peripheral nervous system and also in nonneuronal tissue such as platelet, placental, and pulmonary membranes.…”

“…Although recognizable 5-HTT homologues, based on nucleotide sequences, have been found to be expressed near-ubiquitously in animal phyla, 39 the regulation and properties of the transporter protein may be diverse. Therefore, functional experiments are required to characterize the 5-HT transport mechanism in different species.…”

Investigating candidate neuromodulatory systems underlying parasitic manipulation: concepts, limitations and prospects

“…According to the psychoneuroimmune hypothesis of parasitic manipulation (Adamo, 2002;Helluy, 2013), these properties of the neural and immune systems have probably been hijacked by parasites with the ultimate consequence of increasing their transmission. (3) A parsimonious evolutionary argument, considering that the phylogenetic conservatism of neuromodulatory, signalling and immune systems may facilitate a molecular cross-talk between the parasite and the host (Salzet et al, 2000;Maier 2003;Caveney et al, 2006). For instance, the increased dopaminergic activity in some area of the brain of T. gondii-infected mice is due to the release by the parasite's cyst itself of the rate-limiting enzyme in dopamine synthesis (Prandovszky et al, 2011).…”