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The calcineurin-NFATc4 pathway is critical for neuritin to promote Kv4.2 transcription

The calcineurin-NFATc4 pathway is critical for neuritin to p...

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中国神经科学学会第十届全国学术会议

作者： Jin-Jing YAO Xiao-Qin ZHAN Qian-Ru ZHAO Yan-Ai MEI Institutes of Brain Science School of Life Sciences and State Key Laboratory of Medical NeurobiologyFudan University

Objective Neuritin is a new neurotrophic factor discovered in a screen to identify genes involved in activity-dependent synaptic *** also plays multiple roles in the process of neural development and synaptic *** previous work had reported that Neuritin increases Kv4.2-mediated I in rat cerebellar granule neurons by activating insulin receptor pathway and up-regulated the transcription and translation of ***,the mechanisms how Neuritin could promote Kv4.2 transcription is still not ***,we try to fig out whether the calcineurin-NFATc4 pathway is involved in the function of *** By using specific chemical inhibitors against Calcineurin,Cyclosporin A(CsA) and FK520,to block Calcineurin-NFATc4 pathway to find out whether it could offset the increase of Kv4.2 expression and I density caused by *** using NFATc4 mice,we found whether this transcription factor is important for Neuritin to regulate Kv4.2 ***,we isolated Kv4.2promoter and cloned it into the pGL3-Enhancer Vector to study whether Neuritin could increase the activation of ***(1)Calcineurin inhibitors could block Neuritin’s function on up-regulating Kv4.2 expression(CsA:from 45.5±5.7%to 5.1±3.2%;FK520:from 45.5±5.7%to 10.7±4.1%) and I density(CsA:from 53.8±6.7%to7.1±3.9%;FK520:from 53.8±6.7%to 16.9±5.3%).(2) In NFATC4" mice’s cerebellar granule cells Neuritin could not increase Kv4.2 expression and I *** incubating with Neuritin,Kv4.2 expression was increased 3.01+1.8%,I density was increased 5.89+3.1%,there is no significant difference compared with control group.(3) The Kv4.2promoter sequence has been *** The Calcineurin-NFATc4 pathway is critical for Neuritin to promote Kv4.2 *** are trying to find out the mechanism under this modulation.

关键词： calcineurin-NFATc4 pathway neuritin Kv4.2 IA cerebellar granule cells

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