Regulation of the Neuronal Taurine Transporter Protein

Abstract

<p>Cytotoxic brain edema occurs in a variety of pathological conditions. Net efflux of the amino acid taurine from neurons contributes to neuronal volume regulation during brain edema. Taurine is accumulated in both neurons and glial cells by a specific 72-75 kDa membrane transporter, TauT. Neuronal and glial forms of TauT are similar in structure; however, functional TauT activity decreases in swollen neurons, but is not altered in swollen astroglial cells. In contrast, activation of protein kinase-C (PKC) has no effect on neuronal TauT activity, but causes protein phosphorylation and inhibits the transporter in astroglial cells. Thus, we hypothesize that regulation of neuronal and glial TauT is mediated by different signaling mechanisms. Methods: Primary neuronal cultures from rat hippocampus were incubated under isoosmotic or hypoosmotic conditions. After 30 min we measured total and sub-cellular TauT expression using cell fractionation and western blot analysis. Results: In control neurons, TauT appeared as a 97 kDa peptide in cytosolic and membrane/particulate fractions. However, in neuronal cultures treated with hypoosmotic medium the density of the TauT band was significantly reduced in the cytosolic and membrane/particulate fractions while a prominent 74 kDa band appeared in the nuclear fraction. Total TauT expression was not altered by hypoosmotic exposure. Conclusion: TauT in normal cultured hippocampal neurons may be substantially glycosylated or closely associated with other peptides while in the plasma membrane. The apparent molecular weight of TauT is reduced in swollen neurons while it is redistributed from the cell membrane to the nucleus. Internalization of the transporter from the plasma membrane may account for the reduction in functional TauT transport activity observed in swollen neurons and may contribute to neuronal volume regulation.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>