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Title: Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons
Author: Chen, Xu-Qiao ; Wang, Bin ; Wu, Chengbiao ; Pan, Jin ; Yuan, Bo ; Su, Yuan-Yuan ; Jiang, Xing-Yu ; null(张 旭) ; Bao, Lan
Source: CELL RESEARCH
Issued Date: 2012
Volume: 22, Issue:4, Pages:677-696
Keyword: P2X(3) receptor ; retrograde transport ; Rab7 ; signaling endosomes ; lipid raft ; NERVE GROWTH-FACTOR ; NEUROPATHIC PAIN ; LIPID RAFTS ; PHOSPHORYLATED ERK ; INFLAMMATORY PAIN ; MOLECULAR MOTORS ; MICE LACKING ; FACTOR CREB ; ATP ; BINDING
Subject: Cell Biology
Corresponding Author: Bao, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China,baolan@sibs.ac.cn
English Abstract: Neurotrophins and their receptors adopt signaling endosomes to transmit retrograde signals. However, the mechanisms of retrograde signaling for other ligand/receptor systems are poorly understood. Here, we report that the signals of the purinergic (P)2X(3) receptor, an ATP-gated ion channel, are retrogradely transported in dorsal root ganglion (DRG) neuron axons. We found that Rab5, a small GTPase, controls the early sorting of P2X(3) receptors into endosomes, while Rab7 mediates the fast retrograde transport of P2X(3) receptors. Intraplantar injection and axonal application into the microfluidic chamber of alpha, beta-methylene-ATP (alpha, beta-MeATP), a P2X selective agonist, enhanced the endocytosis and retrograde transport of P2X(3) receptors. The alpha, beta-MeATP-induced Ca2+ influx activated a pathway comprised of protein kinase C, rat sarcoma viral oncogene and extracellular signal-regulated protein kinase (ERK), which associated with endocytic P2X(3) receptors to form signaling endosomes. Disruption of the lipid rafts abolished the alpha, beta-MeATP-induced ERK phosphorylation, endocytosis and retrograde transport of P2X(3) receptors. Furthermore, treatment of peripheral axons with alpha, beta-MeATP increased the activation level of ERK and cAMP response element-binding protein in the cell bodies of DRG neurons and enhanced neuronal excitability. Impairment of either microtubule-based axonal transport in vivo or dynein function in vitro blocked alpha, beta-MeATP-induced retrograde signals. These results indicate that P2X(3) receptor-activated signals are transmitted via retrogradely transported endosomes in primary sensory neurons and provide a novel signaling mechanism for ligand-gated channels.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1492
Appears in Collections:神经所(总)_期刊论文
感觉系统研究组_期刊论文

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Chen, Xu-Qiao; Wang, Bin; Wu, Chengbiao; Pan, Jin; Yuan, Bo; Su, Yuan-Yuan; Jiang, Xing-Yu; Zhang, Xu; Bao, Lan.Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons,CELL RESEARCH,2012,22(4):677-696
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