Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons

	Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons
	Chen, XQ; Wang, B; Wu, CB; Pan, J; Yuan, B; Su, YY; Jiang, XY; Zhang, X; Bao, L
刊名	CELL RESEARCH
	2012
卷号	22 期号:4 页码:677-696
关键词	P2X(3) receptor retrograde transport Rab7 signaling endosomes lipid raft
通讯作者	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
英文摘要	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.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	NERVE GROWTH-FACTOR ; NEUROPATHIC PAIN ; LIPID RAFTS ; PHOSPHORYLATED ERK ; INFLAMMATORY PAIN ; MOLECULAR MOTORS ; MICE LACKING ; FACTOR CREB ; ATP ; BINDING
收录类别	SCI
语种	英语
WOS记录号	WOS:000302351800009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/577]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chen, XQ,Wang, B,Wu, CB,et al. Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons[J]. CELL RESEARCH,2012,22(4):677-696.
APA	Chen, XQ.,Wang, B.,Wu, CB.,Pan, J.,Yuan, B.,...&Bao, L.(2012).Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons.CELL RESEARCH,22(4),677-696.
MLA	Chen, XQ,et al."Endosome-mediated retrograde axonal transport of P2X(3) receptor signals in primary sensory neurons".CELL RESEARCH 22.4(2012):677-696.