Evidence map›Paper›PMID 19136557›Full record

ArticleThe Journal of biological chemistry2009

Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.

Michael D Carrithers, Gouri Chatterjee, Lisette M Carrithers, Roosevelt Offoha, Uzoma Iheagwara, Christoph Rahner, Morven Graham, Stephen G Waxman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

59 citing papers in PubMed, 113 citations in OpenAlex.

  1. Potential therapeutic targeting of BKMolecular oncology · 2026
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  6. Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. The voltage-gated KPlatelets · 2022
    Article
  12. The Role of Calcium Signaling in Melanoma.International journal of molecular sciences · 2022
    Review
  13. Article
  14. Review
  15. Article
  16. Article
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  18. Article
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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

8 authors at 2 institutions in 1 country.

Michael D CarrithersDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520-8018, USA. carrithers@neurology.wisc.edu
Gouri Chatterjee
Lisette M Carrithers
Roosevelt Offoha
Uzoma Iheagwara
Christoph Rahner
Morven Graham
Stephen G Waxman
Yale University · USVA Connecticut Healthcare System · US

Funding

CD8 T Lymphocyte Regulation of EAE Disease PhenotypeK02NS047457 · NINDS · YALE UNIVERSITY · PI CARRITHERS, MICHAEL D · 2004 to 2008
$756k
NINDS NIH HHS K02 NS047457
6 · The paper itself

Abstract

Voltage-gated sodium channels initiate electrical signaling in excitable cells such as muscle and neurons. They also are expressed in non-excitable cells such as macrophages and neoplastic cells. Previously, in macrophages, we demonstrated expression of SCN8A, the gene that encodes the channel NaV1.6, and intracellular localization of NaV1.6 to regions near F-actin bundles, particularly at areas of cell attachment. Here we show that a splice variant of NaV1.6 regulates cellular invasion through its effects on podosome and invadopodia formation in macrophages and melanoma cells. cDNA sequence analysis of SCN8A from THP-1 cells, a human monocyte-macrophage cell line, confirmed the expression of a full-length splice variant that lacks exon 18. Immunoelectron microscopy demonstrated NaV1.6-positive staining within the electron dense podosome rosette structure. Pharmacologic antagonism with tetrodotoxin (TTX) in differentiated THP-1 cells or absence of functional NaV1.6 through a naturally occurring mutation (med) in mouse peritoneal macrophages inhibited podosome formation. Agonist-mediated activation of the channel with veratridine caused release of sodium from cationic vesicular compartments, uptake by mitochondria, and mitochondrial calcium release through the Na/Ca exchanger. Invasion by differentiated THP-1 and HTB-66 cells, an invasive melanoma cell line, through extracellular matrix was inhibited by TTX. THP-1 invasion also was inhibited by small hairpin RNA knockdown of SCN8A. These results demonstrate that a variant of NaV1.6 participates in the control of podosome and invadopodia formation and suggest that intracellular sodium release mediated by NaV1.6 may regulate cellular invasion of macrophages and melanoma cells.

Indexed as

Alternative SplicingAnimalsCalciumCell DifferentiationCell Line, TumorCell Membrane StructuresExonsHumansMacrophages, PeritonealMelanomaMiceMice, Mutant StrainsMitochondriaMutationNAV1.6 Voltage-Gated Sodium ChannelNeoplasm InvasivenessCalciumNAV1.6 Voltage-Gated Sodium ChannelNerve Tissue ProteinsSCN8A protein, humanScn8a protein, mouseSodium Channel BlockersSodium ChannelsTetrodotoxinVeratridine

Identifiers

PMID19136557
PMCPMC2658105
OpenAlexW2166236894

What OpenQuestion holds

Textmetadata
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.