Spinophilin-Targeted Protein Phosphatase-1 Alleviated Inflammatory Pain by Negative Control of MEK/ERK Signaling in Spinal Cord Dorsal Horn of Rats

doi:10.1523/JNEUROSCI.2293-15.2015

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	Spinophilin-Targeted Protein Phosphatase-1 Alleviated Inflammatory Pain by Negative Control of MEK/ERK Signaling in Spinal Cord Dorsal Horn of Rats
	Hu, XD; Liu, YN; Zhang, ZY; Ma, ZA; Suo, ZW; Yang, X; Hu, XD (reprint author), Lanzhou Univ, Dept Mol Pharmacol, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China.
刊名	JOURNAL OF NEUROSCIENCE
	2015-10-14
卷号	35 期号:41 页码:13989-14001
关键词	extracellular signal-regulated kinase NMDA receptor pain protein phosphatase-1 spinophilin
ISSN号	0270-6474
DOI	10.1523/JNEUROSCI.2293-15.2015
文献子类	Article
英文摘要	Protein phosphatase-1 (PP1), anchored by regulatory or targeting proteins at excitatory glutamatergic synapses, controls the phosphorylation of postsynaptic substrates and regulates the neurotransmission and plasticity. Here, we found that spinophilin, an actin-binding protein that targets PP1 at postsynaptic density, served as a scaffold for extracellular signal-regulated kinase (ERK) signaling components. Through the C-terminal PDZ domain, spinophilin directly interacted with ERK and its upstream mitogen-activated protein kinase kinase (MEK). PP1, recruited by spinophilin, gained access to and dephosphorylated these kinases, exerting a tonic inhibition of ERK signaling. The removal of PP1 inhibition by disturbing spinophilin/PP1 interaction allowed a restricted activation of MEK/ERK at synapses, which in turn augmented the synaptic transmission specifically mediated by GluN2B subunit-containing N-methyl-D-aspartate subtype of glutamate receptors. We provided evidence that in pain-related spinal cord dorsal horn, the scaffolding function of spinophilin played an important role in the negative control of ERK-dependent and GluN2B-dependent pain sensitization. Expression of wild-type spinophilin produced an effective analgesic action against chronic inflammatory pain induced by complete Freund's adjuvant in rats.
学科主题	Neurosciences & Neurology
出版地	WASHINGTON
资助项目	国家自然科学基金项目
项目编号	National Natural Science Foundation of China [30870837, 31271186]
语种	英语
WOS记录号	WOS:000366051800019
资助机构	NSFC
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/179563]
专题	药学院_期刊论文
通讯作者	Hu, XD (reprint author), Lanzhou Univ, Dept Mol Pharmacol, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China.
推荐引用方式 GB/T 7714	Hu, XD,Liu, YN,Zhang, ZY,et al. Spinophilin-Targeted Protein Phosphatase-1 Alleviated Inflammatory Pain by Negative Control of MEK/ERK Signaling in Spinal Cord Dorsal Horn of Rats[J]. JOURNAL OF NEUROSCIENCE,2015,35(41):13989-14001.
APA	Hu, XD.,Liu, YN.,Zhang, ZY.,Ma, ZA.,Suo, ZW.,...&Hu, XD .(2015).Spinophilin-Targeted Protein Phosphatase-1 Alleviated Inflammatory Pain by Negative Control of MEK/ERK Signaling in Spinal Cord Dorsal Horn of Rats.JOURNAL OF NEUROSCIENCE,35(41),13989-14001.
MLA	Hu, XD,et al."Spinophilin-Targeted Protein Phosphatase-1 Alleviated Inflammatory Pain by Negative Control of MEK/ERK Signaling in Spinal Cord Dorsal Horn of Rats".JOURNAL OF NEUROSCIENCE 35.41(2015):13989-14001.