Vesicular nucleotide transporter is involved in ATP storage of secretory lysosomes in astrocytes |
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Authors: | Manami Oya Tetsuya Kitaguchi Yu Yanagihara Rika Numano Masaki Kakeyama Kazuya Ikematsu Takashi Tsuboi |
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Affiliation: | 1. Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan;2. Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABIOS), Waseda University, 11 Biopolis Way, #05-01/02 Helios, Singapore 138667, Singapore;3. The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tennpaku-cho, Toyohashi, Aichi 441-8580, Japan;4. Department of Neurobiology and Behavior Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan;5. Forensic Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan |
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Abstract: | Recent studies have suggested that astrocytes release gliotransmitters (i.e., ATP, L-glutamate, D-serine, and peptide hormones) and participate actively in synaptic functioning. Although ATP release from astrocytes modulates the activity of neurons, the mechanisms regulating the ATP release from astrocytes and the source of ATP in astrocytes are not well understood. Recently a vesicular nucleotide transporter (VNUT)/solute carrier family 17, member 9 (SLC17A9) has been identified as a mediator of the active accumulation of ATP into vesicles. Here we show by immunocytochemical analysis under confocal microscope and live cell imaging under total internal reflection fluorescence microscope that lysosome-associated VNUT is responsible for ATP release in astrocytes. VNUT was expressed in both primary cultured cortical astrocytes and glioma cell line C6 cells, and mainly localized on lysosome in the cells. We found that VNUT-associated secretory lysosomes do not fully collapse into the plasma membrane after lysosomal exocytosis. We also found that inhibition of VNUT function by Evans Blue decreased ATP uptake into secretory lysosomes. Depletion and inhibition of endogenous VNUT by small interference RNA and Evans Blue, respectively decreased the amount of ATP release from the cells, whereas overexpression of VNUT increased it. Taken together, these findings indicate that the participation of VNUT in ATP storage in secretory lysosomes during lysosomal exocytosis of ATP from astrocytes. |
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Keywords: | Astrocytes ATP Exocytosis Lysosome Vesicular nucleotide transporter |
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