ArticleThe Journal of biological chemistry2015
Amyloid precursor protein enhances Nav1.6 sodium channel cell surface expression.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies.Ageing research reviews · 2022Pooled it
- Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury.Neural regeneration research · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Amyloid precursor protein modulates cerebellar Purkinje cell activity and motor function through regulation of Nav1.6 currents.PLoS biology · 2025Article
- Inhibition of the GSK3β/Nav1.6 complex suppresses early-stage Alzheimer's hyperexcitability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Abnormality of Voltage-Gated Sodium Channels in Disease Development of the Nervous System. A Review Article.CNS & neurological disorders drug targets · 2025Review
- Alzheimer's-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice.Brain research · 2024Article
- Voltage-Gated NaLife (Basel, Switzerland) · 2023Review
- Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders.Life (Basel, Switzerland) · 2023Review
- Review
- Homeostatic plasticity of axonal excitable sites in Alzheimer's disease.Frontiers in neuroscience · 2023Article
- An unbiased algorithm for objective separation of Alzheimer's, Alzheimer's mixed with cerebrovascular symptomology, and healthy controls from one another using electrovestibulography (EVestG).Medical & biological engineering & computing · 2022Article
- Functional Neurophysiological Biomarkers of Early-Stage Alzheimer's Disease: A Perspective of Network Hyperexcitability in Disease Progression.Journal of Alzheimer's disease : JAD · 2022Review
- Physiological separation of Alzheimer's disease and Alzheimer's disease with significant levels of cerebrovascular symptomology and healthy controls.Medical & biological engineering & computing · 2021Article
- Review
- Analysis of Age-Dependent Alterations in Excitability Properties of CA1 Pyramidal Neurons in an APPPS1 Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- Article
- Amyloid β-Induced Upregulation of NaScientific reports · 2019Article
- APP upregulation contributes to retinal ganglion cell degeneration via JNK3.Cell death and differentiation · 2018Article
- Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus.The Journal of comparative neurology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid precursor protein (APP) is commonly associated with Alzheimer disease, but its physiological function remains unknown. Nav1.6 is a key determinant of neuronal excitability in vivo. Because mouse models of gain of function and loss of function of APP and Nav1.6 share some similar phenotypes, we hypothesized that APP might be a candidate molecule for sodium channel modulation. Here we report that APP colocalized and interacted with Nav1.6 in mouse cortical neurons. Knocking down APP decreased Nav1.6 sodium channel currents and cell surface expression. APP-induced increases in Nav1.6 cell surface expression were Go protein-dependent, enhanced by a constitutively active Go protein mutant, and blocked by a dominant negative Go protein mutant. APP also regulated JNK activity in a Go protein-dependent manner. JNK inhibition attenuated increases in cell surface expression of Nav1.6 sodium channels induced by overexpression of APP. JNK, in turn, phosphorylated APP. Nav1.6 sodium channel surface expression was increased by T668E and decreased by T668A, mutations of APP695 mimicking and preventing Thr-668 phosphorylation, respectively. Phosphorylation of APP695 at Thr-668 enhanced its interaction with Nav1.6. Therefore, we show that APP enhances Nav1.6 sodium channel cell surface expression through a Go-coupled JNK pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.