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The taurine transporter: mechanisms of regulation
Author(s) -
Han X.,
Patters A. B.,
Jones D. P.,
Zelikovic I.,
Chesney R. W.
Publication year - 2006
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2006.01573.x
Subject(s) - taurine , protein kinase c , transactivation , reabsorption , chemistry , gene expression , phosphorylation , biology , biochemistry , amino acid , microbiology and biotechnology , gene , kidney , endocrinology
Taurine transport undergoes an adaptive response to changes in taurine availability. Unlike most amino acids, taurine is not metabolized or incorporated into protein but remains free in the intracellular water. Most amino acids are reabsorbed at rates of 98–99%, but reabsorption of taurine may range from 40% to 99.5%. Factors that influence taurine accumulation include ionic environment, electrochemical charge, and post‐translational and transcriptional factors. Among these are protein kinase C (PKC) activation and transactivation or repression by proto‐oncogenes such as WT1 , c‐Jun, c‐Myb and p53. Renal adaptive regulation of the taurine transporter (TauT) was studied in vivo and in vitro . Site‐directed mutagenesis and the oocyte expression system were used to study post‐translational regulation of the TauT by PKC. Reporter genes and Northern and Western blots were used to study transcriptional regulation of the taurine transporter gene ( TauT ). We demonstrated that (i) the body pool of taurine is controlled through renal adaptive regulation of TauT in response to taurine availability; (ii) ionic environment, electrochemical charge, pH, and developmental ontogeny influence renal taurine accumulation; (iii) the fourth segment of TauT is involved in the gating of taurine across the cell membrane, which is controlled by PKC phosphorylation of serine 322 at the post‐translational level; (iv) expression of TauT is repressed by the p53 tumour suppressor gene and is transactivated by proto‐oncogenes such as WT1 , c‐Jun, and c‐Myb; and (v) over‐expression of TauT protects renal cells from cisplatin‐induced nephrotoxicity.