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Neuronal cell surface ATP synthase mediates synthesis of extracellular ATP and regulation of intracellular pH

Authors

  • San-Li Xing,

    1. State Key Laboratory of Medical Neurobiology and Department of Neurobiology, Shanghai Medical College, Fudan University, 138 YiXueYuan Road, Shanghai 200032, Peoples Republic of China
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  • Jie Yan,

    1. State Key Laboratory of Medical Neurobiology and Department of Neurobiology, Shanghai Medical College, Fudan University, 138 YiXueYuan Road, Shanghai 200032, Peoples Republic of China
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  • Zhi-Hua Yu,

    1. Shanghai Geriatric Institute of Chinese Medicine, 1199 Central Fuxing Road, Shanghai 200031, Peoples Republic of China
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  • Cui-Qing Zhu

    Corresponding author
    1. State Key Laboratory of Medical Neurobiology and Department of Neurobiology, Shanghai Medical College, Fudan University, 138 YiXueYuan Road, Shanghai 200032, Peoples Republic of China
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To whom correspondence should be addressed (email cqzhu@shmu.edu.cn).

Abstract

The ATP synthase is known to play important roles in ATP generation and proton translocation within mitochondria. Here, we now provide evidence showing the presence of functional ecto-ATP synthase on the neuronal surface. Immunoblotting revealed that the α, β subunits of ATP synthase F1 portion are present in isolated fractions of plasma membrane and biotin-labelled surface protein from primary cultured neurons; the surface distribution of α, β subunits was also confirmed by immunofluorescence staining. Moreover, α and β subunits were also found in fractions of plasma membrane and lipid rafts isolated from rat brain, and flow cytometry analysis showed α subunits on the surface of acutely isolated brain cells. Activity assays showed that the extracellular ATP generation of cultured neurons could be compromised by α, β subunit antibodies and ATP synthase inhibitors. pHi (intracellular pH) analysis demonstrated that at low extracellular pH, α or β subunit antibodies decreased pHi of primary cultured neurons. Therefore, ATP synthase on the surface of neurons may be involved in the machineries of extracellular ATP generation and pHi homoeostasis.

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