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The Journal of Neuroscience, June 24, 2009, 29(25):8063-8074; doi:10.1523/JNEUROSCI.6139-08.2009

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Cellular/Molecular
Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Min Jiang and Gong Chen

Department of Biology, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802

Correspondence should be addressed to Dr. Gong Chen, Department of Biology, 201 Life Sciences Building, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802. Email: gongchen{at}psu.edu

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-β peptide (Aβ) 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 Aβ suggests an important role of the dynamin-independent endocytosis in both physiological and pathological conditions.

Received Dec. 23, 2008; revised April 9, 2009; accepted May 16, 2009.

Correspondence should be addressed to Dr. Gong Chen, Department of Biology, 201 Life Sciences Building, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802. Email: gongchen{at}psu.edu






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