Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep39320
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dc.titleAmyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway
dc.contributor.authorLi, S
dc.contributor.authorWang, X
dc.contributor.authorMa, Q.-H
dc.contributor.authorYang, W.-L
dc.contributor.authorZhang, X.-G
dc.contributor.authorDawe, G.S
dc.contributor.authorXiao, Z.-C
dc.date.accessioned2020-10-21T08:13:10Z
dc.date.available2020-10-21T08:13:10Z
dc.date.issued2016
dc.identifier.citationLi, S, Wang, X, Ma, Q.-H, Yang, W.-L, Zhang, X.-G, Dawe, G.S, Xiao, Z.-C (2016). Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway. Scientific Reports 6 : 39320. ScholarBank@NUS Repository. https://doi.org/10.1038/srep39320
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178743
dc.description.abstractAmyloid precursor protein (APP), commonly associated with Alzheimer's disease, also marks axonal degeneration. In the recent studies, we demonstrated that APP aggregated at nodes of Ranvier (NORs) in myelinated central nervous system (CNS) axons and interacted with Nav1.6. However, the physiological function of APP remains unknown. In this study, we described reduced sodium current densities in APP knockout hippocampal neurons. Coexpression of APP or its intracellular domains containing a VTPEER motif with Na v 1.6 sodium channels in Xenopus oocytes resulted in an increase in peak sodium currents, which was enhanced by constitutively active Go mutant and blocked by a dominant negative mutant. JNK and CDK5 inhibitor attenuated increases in Nav1.6 sodium currents induced by overexpression of APP. Nav1.6 sodium currents were increased by APPT668E (mutant Thr to Glu) and decreased by T668A (mutant Thr to ALa) mutant, respectively. The cell surface expression of Nav1.6 sodium channels in the white matter of spinal cord and the spinal conduction velocity is decreased in APP, p35 and JNK3 knockout mice. Therefore, APP modulates Nav1.6 sodium channels through a Go-coupled JNK pathway, which is dependent on phosphorylation of APP at Thr668. © 2016 The Author(s).
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectamyloid precursor protein
dc.subjectinhibitory guanine nucleotide binding protein
dc.subjectScn8a protein, mouse
dc.subjectsodium channel Nav1.6
dc.subjectanimal
dc.subjecthippocampus
dc.subjectknockout mouse
dc.subjectMAPK signaling
dc.subjectmetabolism
dc.subjectnerve cell
dc.subjectphosphorylation
dc.subjectphysiology
dc.subjectprotein processing
dc.subjectXenopus
dc.subjectAmyloid beta-Protein Precursor
dc.subjectAnimals
dc.subjectGTP-Binding Protein alpha Subunits, Gi-Go
dc.subjectHippocampus
dc.subjectMAP Kinase Signaling System
dc.subjectMice, Knockout
dc.subjectNAV1.6 Voltage-Gated Sodium Channel
dc.subjectNeurons
dc.subjectPhosphorylation
dc.subjectProtein Processing, Post-Translational
dc.subjectXenopus
dc.typeArticle
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.1038/srep39320
dc.description.sourcetitleScientific Reports
dc.description.volume6
dc.description.page39320
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