The Biotechnology Center and Center for Molecular Biology and Neuroscience, University of Oslo, Blindern, Oslo, Norway.
Glia. 2012 Nov;60(11):1671-83. doi: 10.1002/glia.22386. Epub 2012 Jul 20.
Activation of NMDA receptor requires two co-agonists, glutamate and glycine. Despite its intrinsic role in brain functions molecular mechanisms involved in glutamate replenishment and identification of the origin of glycine have eluded characterization. We have performed direct measurements of glycine flux by SN2 (Slc38a5; also known as SNAT5), executed extensive electrophysiological characterization as well as implemented ratiometric analyses to show that SN2 transport resembles SN1 in mechanism but differ in functional implications. We report that rat SN2 mediates electroneutral and bidirectional transport of glutamine and glycine at perisynaptic astroglial membranes. Sophisticated coupled and uncoupled movements of H(+) differentially associate with glutamine and glycine transport by SN2 and regulate pH(i) and the release mode of the transporter. Consequently, SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors.
NMDA 受体的激活需要两种共激动剂，谷氨酸和甘氨酸。尽管它在大脑功能中具有内在作用，但参与谷氨酸补充的分子机制以及甘氨酸的来源仍未得到阐明。我们通过 SN2（Slc38a5；也称为 SNAT5）进行了甘氨酸通量的直接测量，执行了广泛的电生理特性分析，并进行了比率分析，以表明 SN2 转运在机制上类似于 SN1，但在功能意义上有所不同。我们报告说，大鼠 SN2 在突触前星形胶质细胞膜上介导谷氨酰胺和甘氨酸的电中性和双向转运。H(+)的复杂偶联和非偶联运动与 SN2 的谷氨酰胺和甘氨酸转运不同，调节 pH(i)和转运体的释放模式。因此，SN2 兼具神经递质前体供应者和 NMDA 受体潜在调节剂的双重功能。
