Regulated ATP release from astrocytes through lysosome exocytosis

• Published in: Nature cell biology Vol. 9; no. 8; pp. 945 - 953
• Main Authors: Xu, Tao, Zhang, Zhijun, Duan, Shumin, Song, Aihong, Zhou, Wei, Gu, Xiao-song, Chen, Gang, Wang, Wei, Luo, Qingming
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-08-2007
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Animals; Animals, Newborn; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; ATP; Biomarkers - metabolism; Calcium Signaling; Cells, Cultured; Dyes; Exocytosis; Exocytosis - physiology; Fluorescence; Fluorescence microscopy; Fluorescent Dyes - metabolism; Hippocampus - cytology; Hippocampus - metabolism; Laboratories; Localization; Lysosomal-Associated Membrane Protein 1 - genetics; Lysosomal-Associated Membrane Protein 1 - metabolism; Lysosomes; Lysosomes - metabolism; Lysosomes - ultrastructure; Microscopy; Neurosciences; Physiological aspects; Physiology; Potassium Cyanide - metabolism; Propagation; Pyridinium Compounds - metabolism; Quaternary Ammonium Compounds - metabolism; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Wave propagation; China
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb1620

Release of ATP from astrocytes is required for Ca2+ wave propagation among astrocytes and for feedback modulation of synaptic functions. However, the mechanism of ATP release and the source of ATP in astrocytes are still not known. Here we show that incubation of astrocytes with FM dyes leads to selective labelling of lysosomes. Time-lapse confocal imaging of FM dye-labelled fluorescent puncta, together with extracellular quenching and total-internal-reflection fluorescence microscopy (TIRFM), demonstrated directly that extracellular ATP or glutamate induced partial exocytosis of lysosomes, whereas an ischaemic insult with potassium cyanide induced both partial and full exocytosis of these organelles. We found that lysosomes contain abundant ATP, which could be released in a stimulus-dependent manner. Selective lysis of lysosomes abolished both ATP release and Ca2+ wave propagation among astrocytes, implicating physiological and pathological functions of regulated lysosome exocytosis in these cells.