Ca²⁺ regulation of dynamin-independent endocytosis in cortical astrocytes

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.