Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes
Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes
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DOI：
10.1523/jneurosci.6139-08.2009
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发表时间：
2009-06-24
影响因子：
5.3
通讯作者：
Chen, Gong
中科院分区：
文献类型：
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作者：
Jiang, Min;Chen, Gong
星形胶质细胞通过囊泡胞吐作用释放ATP和谷氨酸来介导神经元-胶质细胞相互作用。与胞吐作用相反，星形胶质细胞的内吞途径知之甚少。在这里，我们确定了一个组成性的内吞途径，在培养的星形胶质细胞，既不依赖网格蛋白，也不发动蛋白。这种不依赖动力蛋白的内吞途径受Rab 5（一种早期内体蛋白）的调节。内吞的囊泡显示出在几分钟内从早期内体到晚期内体和溶酶体的快速转变。有趣的是，星形胶质细胞中的这种网格蛋白和动力蛋白独立的内吞作用受到细胞内Ca 2+的有力调控。ATP和谷氨酸通过升高胞内Ca ~（2+）而增强非动力蛋白依赖性内吞作用。此外，淀粉样蛋白-β肽（A β）还通过诱导星形胶质细胞中的Ca 2+瞬变来增强动力蛋白非依赖性内吞作用。这些结果表明，在神经胶质细胞中的一种新的内吞途径，是动力蛋白独立的，但受到细胞内Ca 2+的严格调控。ATP、谷氨酸和A β的调节表明非动力蛋白依赖性内吞在生理和病理条件下都具有重要作用。
Astrocytes release ATP and glutamate through vesicular exocytosis to mediate neuron-glial interactions. In contrast to exocytosis, the endocytic pathways in astroglial cells are poorly understood. Here, we identify a constitutive endocytic pathway in cultured astrocytes that is dependent on neither clathrin nor dynamin. This dynamin-independent endocytic pathway is regulated by Rab5, an early endosome protein. The endocytosed vesicles show fast transition from early endosomes to late endosomes and lysosomes within a few minutes. Interestingly, this clathrin- and dynamin-independent endocytosis in astrocytes is potently regulated by intracellular Ca2+. ATP and glutamate greatly enhance the dynamin-independent endocytosis through elevating the intracellular Ca2+. In addition, amyloid-beta peptide (A beta) also enhances the dynamin-independent endocytosis by inducing Ca2+ transients in astrocytes. These results demonstrate a novel endocytic pathway in glial cells that is dynamin independent but tightly regulated by intracellular Ca2+. The regulation by ATP, glutamate, and A beta suggests an important role of the dynamin-independent endocytosis in both physiological and pathological conditions.