Immunocytochemical Approaches to the Identification of Membrane Topology of the Na+/Cl--Dependent Neurotransmitter Transporters

Abstract

Transporters, located in the cell surface plasma membrane and intracellular organelle membrane, compose a major class of integral membrane proteins, as distinguished with their specialized functions as channels and receptors. They are divided into two groups of gene family; one is the solute carrier (SLC) super family and the other is the ATP-binding cassette (ABC) gene family (Giacomini & Sugiyama, 2006). The transporters for neurotransmitters in the plasma membrane, which belong to the SLC6 gene family, terminate synaptic neurotransmission by Na+/Cl--dependent uptake of released neurotransmitters into the neuronal and/or glial cells (Iversen, 1971). They are responsible for the reuptake not only of neurotransmitters, monoamines (dopamine (DA), noradrenaline (NA), and serotonin (5-HT)) and amino acids (-aminobutyric acid (GABA) and glycine), but also of neuromodulators and/or osmolytes (proline, taurine, betaine, and creatine). Cloning of their cDNA has facilitated the understanding of the primary structure, gene expression, and their roles in neuronal functions (Amara & Kuhar, 1993). Cellular and molecular aspects of these transporters are needed for the clarification of their physiological and pathological relevance, since it seems likely that alterations of their structure, function and expression produce their anatomical and functional divergence, resulting in an involvement of a number of neurological and psychiatric disorders.