Calcium Triggers Exocytosis from Two Types of Organelles in a Single Astrocyte
Calcium Triggers Exocytosis from Two Types of Organelles in a Single Astrocyte
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钙触发单个星形胶质细胞中两种细胞器的胞吐作用
DOI：
10.1523/jneurosci.6401-10.2011
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发表时间：
2011-07-20
影响因子：
5.3
通讯作者：
Zhou, Zhuan
中科院分区：
文献类型：
--
作者：
Liu, Tao;Sun, Lei;Zhou, Zhuan
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。虽然这些分子的功能，从调节突触传递到控制特定行为，已经被很好地记录下来，但它们的细胞区室的身份仍然不清楚。在这里，我们开始研究小鼠海马星形胶质细胞的囊性胞吐和谷氨酸释放。我们发现小囊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。在相同的星形胶质细胞中，小泡和溶酶体都以Ca2+调节的方式与质膜融合，尽管小泡比溶酶体更有效地胞外化。用梭状芽孢杆菌毒素阻断囊泡谷氨酸转运蛋白或裂解synaptobrevin 2和cellubrevin（两者都是囊泡相关的膜蛋白），极大地抑制了星形胶质细胞的谷氨酸释放，而溶酶体胞外分泌保持不变。因此，小囊泡和溶酶体都有助于Ca2+依赖性囊泡胞吐，小囊泡支持谷氨酸从星形胶质细胞释放。
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 Ca2+-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 Ca2+-dependent vesicular exocytosis, and small vesicles support glutamate release from astrocytes.