Functional Conservation and Genetic Divergence of Chordate Glycinergic Neurotransmission: Insights from Amphioxus Glycine Transporters

Abstract

Glycine is an important neurotransmitter in vertebrates, performing both excitatory and inhibitory actions. Synaptic levels of glycine are tightly controlled by the action of two glycine transporters, GlyT1 and GlyT2, located on the surface of glial cells and neurons, respectively. Only limited information is available on glycinergic neurotransmission in invertebrates, and the evolution of glycinergic neurotransmission is poorly understood. Here, by combining phylogenetic and gene expression analyses, we characterized the glycine transporter complement of amphioxus, an important invertebrate model for studying the evolution of chordates. We show that amphioxus possess three glycine transporter genes. Two of these (GlyT2.1 and GlyT2.2) are closely related to GlyT2 of vertebrates, whereas the third (GlyT) is a member of an ancestral clade of deuterostome glycine transporters. GlyT2.2 expression is predominantly non-neural, whereas GlyT and GlyT2.1 are widely expressed in the amphioxus nervous system and are differentially expressed, respectively, in neurons and glia. Vertebrate glycinergic neurons express GlyT2 and glia GlyT1, suggesting that the evolution of the chordate glycinergic system was accompanied by a paralog-specific inversion of gene expression. Despite this genetic divergence between amphioxus and vertebrates, we found strong evidence for conservation in the role glycinergic neurotransmission plays during larval swimming, the implication being that the neural networks controlling the rhythmic movement of chordate bodies may be homologous.

Molecular and cellular basis of life cycle transition provides new insights into ecological adaptation in jellyfish

“…Retinal neurons play a crucial role in visual perception, enabling organisms to detect changes in light and navigate their environment, thereby facilitating essential behaviours. 31,46 Glycinergic neurons, through the coordinated actions of GlyT2 and VIAAT proteins, play a vital role in the nervous system by maintaining the balance of excitatory and inhibitory signalling. 36 Glycinergic neurons regulate rhythmic motor patterns, and related sensory processing has been reported in various organisms, such as amphioxus, 47 ascidians, 48 Xenopus tadpoles, 49 and zebrafish.…”

N-Carbon Quantum Dot/Cu Complex for In Vivo Monitoring of Glycine Levels

“…2 In order to perform these functions, glycine must depolarize the neuronal membrane, store the transmitter in synaptic vesicles, and bind to a particular ligand-gated Cl − channel receptor on the postsynaptic cell. 3 Glycine reuptake is stimulated by the electrochemical gradient of sodium across the plasma membrane, which is upheld by Na + −K + ATPase. The transport of glycine into presynaptic terminals or surrounding glial processes allows the buildup of glycine availability in the synaptic cleft.…”

“…In contrast to its inhibitory function in the brainstem and spinal cord, glycine is specifically involved in the NMDAR and contributes to the function of excitatory glutamatergic synaptic transmission . In order to perform these functions, glycine must depolarize the neuronal membrane, store the transmitter in synaptic vesicles, and bind to a particular ligand-gated Cl – channel receptor on the postsynaptic cell . Glycine reuptake is stimulated by the electrochemical gradient of sodium across the plasma membrane, which is upheld by Na + –K + ATPase.…”

Retinoic Acid and POU Genes in Developing Amphioxus: A Focus on Neural Development

“…Since amphioxus evolves slowly and has a prototypical chordate body plan (reviewed in [9]), it is a key model for understanding chordate diversification and vertebrate evolution. The developing nerve cord of amphioxus, for example, presents homologies to the main regions of the vertebrate central nervous system (CNS) [10][11][12], containing well-characterized neurotransmitter systems [13][14][15][16] and glial cells similar to vertebrate astroglia and radial glia [17]. Amphioxus possesses at least one member of each POU class except class V, which is limited to vertebrates (Table 1) [18].…”