TY - JOUR T1 - A Dominant Role of GTRAP3-18 in Neuronal Glutathione Synthesis JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9404 LP - 9413 DO - 10.1523/JNEUROSCI.3351-08.2008 VL - 28 IS - 38 AU - Masahiko Watabe AU - Koji Aoyama AU - Toshio Nakaki Y1 - 2008/09/17 UR - http://www.jneurosci.org/content/28/38/9404.abstract N2 - Glutathione is an essential reductant which protects cells and is reduced in neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Neurons rely mainly on extracellular cysteine for glutathione synthesis and a cysteine transporter termed excitatory amino acid carrier 1 (EAAC1). However, the mechanisms underlying neuronal cysteine uptake have remained elusive. Herein, we show glutamate transport-associated protein for EAAC1 (GTRAP3-18) to interact with EAAC1 at the plasma membrane and thereby regulate neuronal glutathione levels. Glutathione increased in the mouse brain as well as in primary cultured neurons, when the GTRAP3-18 protein level was decreased by genetic manipulations, whereas glutathione decreased when GTRAP3-18 was increased. Furthermore, glutathione contents that had been increased, by a translocator and activator of EAAC1, were suppressed by increased cell surface GTRAP3-18 protein. Our results demonstrate GTRAP3-18 to dominantly and negatively determine the intracellular glutathione contents in neurons. ER -