Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Abstract

Cumulative studies showed that taurine (2-aminoethanesulfonic acid) contributes to a variety of physiological events. Transport study suggested the cellular taurine transport in an Na -and Cl -dependent manner, and the several members of SLC6A family have been shown as taurine transporter. At the inner blood-retinal barrier (BRB), taurine transporter (TauT/SLC6A) is involved in the transport of taurine to the retina from the circulating blood. The involvement of TauT is also suggested in γ-aminobutyric acid (GABA) transport at the inner BRB, and its role is assumed in the elimination of GABA from the retinal interstitial fluid. In the retina, taurine is thought to be a major organic osmolyte, and its influx and efflux through TauT and volume-sensitive organic osmolyte and anion channel (VSOAC) in Müller cells regulate the osmolarity in the retinal microenvironment to maintain a healthy retina. In the liver, hepatocytes take up taurine via GABA transporter 2 (GAT2/SLC6A13, the orthologue of mouse GAT3) expressed at the sinusoidal membrane of periportal hepatocytes, contributing to the metabolism of bile acid. Site-directed mutagenesis study suggests amino acid residues that are crucial in the recognition of substrates by GATs and TauT. The evidence suggests the physiological impact of taurine transporters in tissues.

Significance of taurine transporter (TauT) in homeostasis and its layers of regulation (Review)

“…interestingly, differences in the taurine distribution of TauT KO mice were observed, underscoring the complete taurine loss in Kupffer and sinusoidal endothelial cells but not in parenchymal cells (106). For instance, hepatic parenchymal cells of TauT KO mice presented a decline of Tau transporter by 30%, whereas hepatic non-parenchymal cells of TauT KO mice had a marked decline of TauT transporter (52).…”

“…As a general note, TauT transporter expression is ubiquitous ( 49 ), due to the acknowledged function of taurine as an organic osmolyte ( 50 ). The main function of TauT transporter is osmoregulation which contributes to cell volume regulation, utilizing a chemiosmotic Na + gradient to couple ‘downhill’ transport of Na + with ‘uphill’ transport of taurine across the membrane ( 51 ), under isotonic and hypertonic conditions ( 52 ). The external to internal downhill Na + /Cl − gradient determines the uptake of taurine from cells through the action of TauT transporter and taurine is moved through the following stoichiometry 2 Na + :1 taurine:1 Cl − , according to Hill model ( 53 ).…”

Onecut Regulates Core Components of the Molecular Machinery for Neurotransmission in Photoreceptor Differentiation

“…(Scgn-like), ENS_02864 (GTPase Rab11a), and ENS_20001 (FKBP25/3) genes encode for factors involved in different steps of neurotransmission as described in Supplementary Table 2. Interestingly, analysis of genes downregulated in both transgenic conditions revealed the presence of the class 6 transporter family gene ENS_07757 (zebrafish Slc6a4b/mouse Slc6a2), whose vertebrate orthologous genes are expressed in the retina (Norton et al, 2008;Kubo et al, 2016).…”

Uptake Study in Lysosome-Enriched Fraction: Critical Involvement of Lysosomal Trapping in Quinacrine Uptake but Not Fluorescence-Labeled Verapamil Transport at Blood-Retinal Barrier

“…Previous progress in the study of the BRB achieved using in vivo and in vitro methods has demonstrated the critical roles of blood-to-retina transport across the BRB in the retinal homeostasis [ 2 , 3 ]. Furthermore, these studies have clearly shown that nutrient transport at the BRB involves various membrane transporters, such as glucose transporter (GLUT1/SLC2A1), taurine transporter (TAUT/SLC6A6), creatine transporter (CRT/SLC6A8), cationic amino acid transporter (CAT1/SLC7A1), equilibrative nucleoside transporter (ENT2/SLC29A2), and riboflavin transporter (RFVTs/SLC52A) [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”