Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-52882
Sci Rep 2016 Dec 23;6:39320. doi: 10.1038/srep39320.
Show Gene links Show Anatomy links

Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway.

Li S , Wang X , Ma QH , Yang WL , Zhang XG , Dawe GS , Xiao ZC .


Abstract
Amyloid 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 Nav1.6 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.

PubMed ID: 28008944
PMC ID: PMC5180232
Article link: Sci Rep


Species referenced: Xenopus
Genes referenced: apbb1 app cdk5 gchfr mapk8 nav1 tf


Article Images: [+] show captions
References [+] :
Ando, Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. 2001, Pubmed