D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures.
D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures.
复制标题
DOI：
10.1371/journal.pone.0156551
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kavanaugh MP
中科院分区：
文献类型：
--
作者：
Foster AC;Farnsworth J;Lind GE;Li YX;Yang JY;Dang V;Penjwini M;Viswanath V;Staubli U;Kavanaugh MP
N-甲基-D-天冬氨酸（NMDA）受体在突触传递和可塑性中起关键作用。通过突触释放的L-谷氨酸激活NMDA受体还需要甘氨酸或D-丝氨酸占据四聚体受体中的共激动剂结合位点。虽然D-丝氨酸似乎是突触NMDA受体的主要共激动剂，但对脑中D-丝氨酸稳态的转运机制知之甚少。在这项工作中，我们表明，SLC 1氨基酸转运蛋白家族成员SLC 1A 4（ASCT 1）和SLC 1A 5（ASCT 2）介导同源和异源交换的D-丝氨酸与生理相关的动力学参数。此外，在培养的大鼠海马星形胶质细胞中D-丝氨酸摄取的选择性概况与ASCT 1和ASCT 2介导的摄取一致。总之，这些数据表明，SLC 1A 4（ASCT 1）可能代表一个重要的Na-依赖性的D-丝氨酸流量在大脑中，有能力调节细胞外D-丝氨酸，从而NMDA受体活性的途径。
N-methyl-D-aspartate (NMDA) receptors play critical roles in synaptic transmission and plasticity. Activation of NMDA receptors by synaptically released L-glutamate also requires occupancy of co-agonist binding sites in the tetrameric receptor by either glycine or D-serine. Although D-serine appears to be the predominant co-agonist at synaptic NMDA receptors, the transport mechanisms involved in D-serine homeostasis in brain are poorly understood. In this work we show that the SLC1 amino acid transporter family members SLC1A4 (ASCT1) and SLC1A5 (ASCT2) mediate homo- and hetero-exchange of D-serine with physiologically relevant kinetic parameters. In addition, the selectivity profile of D-serine uptake in cultured rat hippocampal astrocytes is consistent with uptake mediated by both ASCT1 and ASCT2. Together these data suggest that SLC1A4 (ASCT1) may represent an important route of Na-dependent D-serine flux in the brain that has the ability to regulate extracellular D-serine and thereby NMDA receptor activity.