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Retrograde-transported endosomes carry P2X3 receptor-activated signals to trigger primary sensory neurons

Retrograde-transported endosomes carry P2X3 receptor-activat...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Xu-Qiao CHEN,Bin WANG,Lan B AO~* Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

＜正＞Objective In nervous system,signals from targets are received at axon terminals and retrogradely transported through signaling endosomes to cell body for regulation of gene *** studies on the retrograde transport of ligand-receptor complex mainly focused on receptors with intrinsic tyrosine kinase activity.A general role of signaling endosomes in retrograde signaling for other receptors needs to be *** we show that retrograde-transported P2X3 receptor,a member of ATP-gated ion channels,couples activated signal *** P2X3 was retrogradely transported which was carried by late endosome and coupled erk pathway molecules in sciatic nerve as well asα,β-MeATP induced erk phosphorylation via P2X3 and endocytosis of P2X3 in which lipid raft was involved,was confirmed by Western blot,immunohistochemistry and live *** physiological and pathological function of the retrograde transport of P2X3 was explored by Western blot,real-time ***（1） P2X3 accumulated at the proximal and distal parts of the ligature in sciatic nerve ligation model.（2） P2X3 positive puncta which co-localized with late endosome marker Rab7 were retrogradely transported in the form of signaling endosomes coupling erk pathway molecules.（3）α,β-MeATP-induced calcium influx caused the endocytosis of P2X3 andα,β-MeATP activated a pkc-ras-raf-mek pathway leading to erk phosphorylation.（4） P2X3 and its signal molecules were detected to reside in lipid raft and lipid raft is involved inα,β-MeATP-induced erk phosphorylation and endocytosis of P2X3.（5） Hindpaw injection of the P2X agonistα,β-MeATP induced the phosphorylation of erk and downstream CREB in dorsal root *** Taken together, this study indicates retrograde-transported endosomes carry P2X3 receptor-activated signals to trigger primary sensory neurons.

关键词： P2X3 late endosome signal endosome pkc-ras-raf-mek-erk lipid raft

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