Function and regulation of taurine transport in Müller cells under osmotic stress

Ando, Daisuke; Kubo, Yoshiyuki; Akanuma, Shin Ichi; Yoneyama, Daisuke; Tachikawa, Masanori; Hosoya, Ken

doi:10.1016/j.neuint.2012.02.018

Cited by 25 publications

(20 citation statements)

References 59 publications

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“…45) Earlier studies showed the transport activity of taurine, the expression of taurine transporters, such as TAUT, GAT1 and GAT3, and high accumulation of taurine in Müller cells, 27,[46][47][48] implying the key role of Müller cells in regulating osmolarity at the retinal ECF. Studies using an in vitro Müller cell model, a conditionally immortalized rat Müller cell line (TR-MUL5 cells), 49,50) suggested that Müller cells are involved in carriermediated taurine transport in an Na + -and Cl − -dependent manner, with a K m value estimated to be 37.9 µM, similar to that of TauT. 4,26,50) In addition, TauT expression detected in primary cultured Müller cells and TR-NUL5 cells 50) supports the involvement of TauT in taurine uptake by Müller cells (Fig.…”

Section: Role Of Taurine Transport In Cell Vol-ume Regulation In the mentioning

confidence: 99%

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

Kubo

Akanuma

Hosoya

2016

Biological & Pharmaceutical Bulletin

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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.

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Section: Role Of Taurine Transport In Cell Vol-ume Regulation In the mentioning

confidence: 99%

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

Kubo

Akanuma

Hosoya

2016

Biological & Pharmaceutical Bulletin

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“…[1][2][3][4]15) However, little is known about the mechanism underlying the differences in substrate specificity between TauT and GATs in term of their sequence similarity. 14,22) The study of LeuT Aa , a bacterial homologue of SLC6A, showed the role of amino acid residues in its function, 24) and the sequence analysis suggested that the four residues in TauT, Gly57, Phe58, Leu306 and Glu406, corresponded to Asn21, Ala22, Phe259 and Ile359 in LeuT Aa (Fig.…”

Section: Discussionmentioning

confidence: 99%

Section: H]taurine and [mentioning

confidence: 99%

“…[1][2][3][4][5] Recent progress in the research of membrane transporter and the blood-retinal barrier (BRB) has revealed the involvement of taurine transporter (TauT/ SLC6A6) in taurine uptake by the retinal capillary endothelial cells and retinal glial cells (Müller cells) contributing to the regulation of retinal osmolarity. 1,2,[6][7][8][9] TauT is expressed in a variety of tissues, such as the retina, brain, liver, placenta and kidney. 10,11) TauT transports taurine (K m =43 µM) in a Na + -and Cl − -dependent manner.…”

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“…15) The physiological importance of TauT is also supported by evidence that the expression of TauT is regulated by the extracellular taurine concentration and osmolarity. 2,[16][17][18][19] TauT belongs to the SLC6A family that includes Na + -and Cl − -dependent neurotransmitter transporters, 11,20) and it is known that members of SLC6A, such as noradrenaline transporter (NET/SLC6A2), dopamine transporter (DAT/SLC6A3), serotonin transporter (SERT/SLC6A4) and creatine transporter (CRT/SLC6A8), play important roles in the central nervous system. GABA transporters (GATs), including GAT1/SLC6A1, GAT2/SLC6A13, GAT3/SLC6A11 and BGT1/SLC6A12, are involved in the transport of GABA by coupling with Na + and Cl − , and exhibit a very similar amino acid sequence (>50%) to TauT.…”

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Amino Acid Residues Involved in the Substrate Specificity of TauT/SLC6A6 for Taurine and γ-Aminobutyric Acid

Yahara

Tachikawa

Akanuma

et al. 2014

Biological & Pharmaceutical Bulletin

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Taurine transporter (TauT/SLC6A6) is an "honorary" γ-aminobutyric acid (GABA) transporter because of its low affinity for GABA. The sequence analysis of TauT implied the role of Gly57, Phe58, Leu306 and Glu406 in the substrate recognition of TauT, and amino acid-substitutions were performed. Immunocytochemistry supported no marked effect of mutations on the expression of TauT. TauT H]taurine and [3 H]GABA uptake, suggesting that Gly57 is involved in the determination of substrate pocket volume and in the interaction with substrates. E406C exhibited a decrease and an increase in the affinity for taurine and GABA, respectively, suggesting the involvement of Glu406 in the substrate specificity of TauT. The inhibition study supported the role of Glu406 in the substrate specificity since [ H]taurine and [3 H]GABA uptake by E406C was less sensitive to taurine and β-alanine, and more sensitive to GABA and nipecotic acid than was the case with wild type of TauT. F58I had an increased affinity for GABA, suggesting the involvement of Phe58 in the substrate accessibility. The kinetic parameters showed the decreased and increased affinities of L306Q for taurine and GABA, respectively, supporting that substrate recognition of TauT is conformationally regulated by the branched-side chain of Leu306. In conclusion, the present results suggest that these residues play important roles in the transport function and substrate specificity of TauT.Key words taurine transporter; TauT (SLC6A6); γ-aminobutyric acid (GABA); GABA transporter (GAT); blood-retinal barrier (BRB)In the retina, taurine (2-aminoethanesulfonic acid) play a role in the protection of the retinal neural cells by acting as an osmolyte and antioxidant. [1][2][3][4][5] Recent progress in the research of membrane transporter and the blood-retinal barrier (BRB) has revealed the involvement of taurine transporter (TauT/ SLC6A6) in taurine uptake by the retinal capillary endothelial cells and retinal glial cells (Müller cells) contributing to the regulation of retinal osmolarity.

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New functions of Müller cells

Reichenbach

Bringmann

2013

Glia

606

464

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Müller cells, the major type of glial cells in the retina, are responsible for the homeostatic and metabolic support of retinal neurons. By mediating transcellular ion, water, and bicarbonate transport, Müller cells control the composition of the extracellular space fluid. Müller cells provide trophic and anti-oxidative support of photoreceptors and neurons and regulate the tightness of the blood-retinal barrier. By the uptake of glutamate, Müller cells are more directly involved in the regulation of the synaptic activity in the inner retina. This review gives a survey of recently discoved new functions of Müller cells. Müller cells are living optical fibers that guide light through the inner retinal tissue. Thereby they enhance the signal/noise ratio by minimizing intraretinal light scattering and conserve the spatial distribution of light patterns in the propagating image. Müller cells act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as soft substrate required for neurite growth and neuronal plasticity. Müller cells release neuroactive signaling molecules which modulate neuronal activity, are implicated in the mediation of neurovascular coupling, and mediate the homeostasis of the extracellular space volume under hypoosmotic conditions which are a characteristic of intense neuronal activity. Under pathological conditions, a subset of Müller cells may differentiate to neural progenitor/stem cells which regenerate lost photoreceptors and neurons. Increasing knowledge of Müller cell function and responses in the normal and diseased retina will have great impact for the development of new therapeutic approaches for retinal diseases.

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Function and regulation of taurine transport in Müller cells under osmotic stress

Cited by 25 publications

References 59 publications

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

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

Amino Acid Residues Involved in the Substrate Specificity of TauT/SLC6A6 for Taurine and γ-Aminobutyric Acid

New functions of Müller cells

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