Letter abstract
Nature Cell Biology 9, 945 - 953 (2007)
Published online: 8 July 2007 | doi:10.1038/ncb1620
Regulated ATP release from astrocytes through lysosome exocytosis
Zhijun Zhang1,6, Gang Chen1,2,6, Wei Zhou1,3,6, Aihong Song1, Tao Xu4, Qingming Luo3, Wei Wang5, Xiao-song Gu2 & Shumin Duan1
Release of ATP from astrocytes is required for Ca2+ wave propagation among astrocytes1, 2, 3 and for feedback modulation of synaptic functions2, 4, 5. 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.
- Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, China.
- Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science & Technology, Wuhan, 430074, China.
- National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
- Department of Neurology, Tongji Hospital, Tongji Medical Scool, Huazhong University of Science and Technology, Wuhan, 430030, China.
- These authors contributed equally to this work.
Correspondence to: Shumin Duan1 e-mail: shumin@ion.ac.cn
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