Evidence map›Paper›PMID 34318654›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2021

The Amyloid Precursor Protein C99 Fragment Modulates Voltage-Gated Potassium Channels.

Rían W Manville, Geoffrey W Abbott

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024
    Article
  6. Article
  7. The Node of Ranvier as an Interface for Axo-Glial Interactions: Perturbation of Axo-Glial Interactions in Various Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Review
  8. Review
  9. Article
  10. Review
  11. Biophysical KeLife · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Rían W ManvilleBioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA.
Geoffrey W AbbottBioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA, abbottg@uci.edu.
BioElectronics (United States) · US

Funding

Therapeutic small molecule modulation of Kv channelsR01NS107671 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Geoffrey W Abbott · 2019 to 2026
$3.1M
NINDS - National Institute of Neurological Disorders and Stroke NS107671-02S1NINDS NIH HHS R01 NS107671
6 · The paper itself

Abstract

BACKGROUND/

aimsThe Amyloid Precursor Protein (APP) is involved in the regulation of multiple cellular functions via protein-protein interactions and has been most studied with respect to Alzheimer's disease (AD). Abnormal processing of the single transmembrane-spanning C99 fragment of APP contributes to the formation of amyloid plaques, which are causally related to AD. Pathological C99 accumulation is thought to associate with early cognitive defects in AD. Here, unexpectedly, sequence analysis revealed that C99 exhibits 24% sequence identity with the KCNE1 voltage-gated potassium (Kv) channel β subunit, comparable to the identity between KCNE1 and KCNE2-5 (21-30%). This suggested the possibility of C99 regulating Kv channels.

methodsWe quantified the effects of C99 on Kv channel function, using electrophysiological analysis of subunits expressed in Xenopus laevis oocytes, biochemical and immunofluorescence techniques.

resultsC99 isoform-selectively inhibited (by 30-80%) activity of a range of Kv channels. Among the KCNQ (Kv7) family, C99 isoform-selectively inhibited, shifted the voltage dependence and/or slowed activation of KCNQ2, KCNQ3, KCNQ2/3 and KCNQ5, with no effects on KCNQ1, KCNQ1-KCNE1 or KCNQ4. C99/APP co-localized with KCNQ2 and KCNQ3 in adult rat sciatic nerve nodes of Ranvier. Both C99 and full-length APP co-immunoprecipitated with KCNQ2 in vitro, yet unlike C99, APP only weakly affected KCNQ2/3 activity. Finally, C99 altered the effects on KCNQ2/3 function of inhibitors tetraethylammounium and XE991, but not openers retigabine and ICA27243.

conclusionOur findings raise the possibility of C99 accumulation early in AD altering cellular excitability by modulating Kv channel activity.

Indexed as

Amino Acid SequenceAmyloid beta-Protein PrecursorAnimalsAnthracenesGene ExpressionHumansKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelKCNQ Potassium ChannelsMembrane PotentialsOocytesPatch-Clamp TechniquesPeptide FragmentsRanvier's NodesRatsRecombinant Proteins10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenoneAmyloid beta-Protein PrecursorAnthracenesAPP protein, humanKCNQ2 Potassium ChannelKcnq2 protein, ratKCNQ3 Potassium ChannelKcnq3 protein, ratKcnq5 protein, ratKCNQ Potassium ChannelsPeptide FragmentsRecombinant ProteinsTetraethylammoniumAlzheimer’s disease; Potassium channel; KCNE; KCNQ2; KCNQ3

Identifiers

PMID34318654
PMCPMC8610427
OpenAlexW3184108007

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.