title: Neuronal cell surface ATP synthase mediates synthesis of extracellular ATP and regulation of intracellular pH.
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. pH(i) (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 pH(i) homoeostasis.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Department of Neurobiology, Shanghai Medical College, Fudan University, 138 YiXueYuan Road, Shanghai 200032, Peoples Republic of China.
authors.forename: San-Li
authors.initials: SL
authors.lastname: Xing
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Yu
authors.forename: Cui-Qing
authors.initials: CQ
authors.lastname: Zhu
mesh_terms: D025181:ATP Synthetase Complexes / Q000502:physiology*; D000136:Acid-Base Equilibrium; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000255:Adenosine Triphosphate; D025181:ATP Synthetase Complexes