State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
J Neurosci. 2011 Jul 20;31(29):10593-601. doi: 10.1523/JNEUROSCI.6401-10.2011.
Astrocytes release a variety of signaling molecules including glutamate, D-serine, and ATP in a regulated manner. Although the functions of these molecules, from regulating synaptic transmission to controlling specific behavior, are well documented, the identity of their cellular compartment(s) is still unclear. Here we set out to study vesicular exocytosis and glutamate release in mouse hippocampal astrocytes. We found that small vesicles and lysosomes coexisted in the same freshly isolated or cultured astrocytes. Both small vesicles and lysosome fused with the plasma membrane in the same astrocytes in a Ca(2+)-regulated manner, although small vesicles were exocytosed more efficiently than lysosomes. Blockade of the vesicle glutamate transporter or cleavage of synaptobrevin 2 and cellubrevin (both are vesicle-associated membrane proteins) with a clostridial toxin greatly inhibited glutamate release from astrocytes, while lysosome exocytosis remained intact. Thus, both small vesicles and lysosomes contribute to Ca(2+)-dependent vesicular exocytosis, and small vesicles support glutamate release from astrocytes.
星形胶质细胞以受调控的方式释放多种信号分子，包括谷氨酸、D-丝氨酸和 ATP。尽管这些分子的功能，从调节突触传递到控制特定行为，都有很好的记录，但它们的细胞区室（s）的身份仍不清楚。在这里，我们着手研究小鼠海马星形胶质细胞中的囊泡胞吐作用和谷氨酸释放。我们发现，小泡和溶酶体在同一新鲜分离或培养的星形胶质细胞中共存。小泡和溶酶体都以 Ca(2+)调节的方式与质膜融合，但小泡比溶酶体更容易胞吐。囊泡谷氨酸转运体的阻断或梭菌毒素对突触融合蛋白 2 和细胞溶素（都是囊泡相关膜蛋白）的切割，极大地抑制了星形胶质细胞中谷氨酸的释放，而溶酶体胞吐作用保持完整。因此，小泡和溶酶体都有助于 Ca(2+)依赖性囊泡胞吐作用，小泡支持星形胶质细胞中谷氨酸的释放。
