Evidence map›Paper›PMID 17626205›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007

Induction of calcium influx through TRPC5 channels by cross-linking of GM1 ganglioside associated with alpha5beta1 integrin initiates neurite outgrowth.

Gusheng Wu, Zi-Hua Lu, Alexander G Obukhov, Martha C Nowycky, Robert W Ledeen

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Cell adhesion and intracellular calcium signaling in neurons.Cell communication and signaling : CCS · 2013
    Pooled it
  2. Article
  3. Article
  4. Gangliosides in Neurodegenerative Diseases.Advances in neurobiology · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Impact of GMBiophysical journal · 2017
    Review
  14. The sugar code in neuronal physiology.Histochemistry and cell biology · 2017
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
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

5 authors at 2 institutions in 2 countries.

Gusheng WuDepartment of Neurology and Neurosciences, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA. gwu@umdnj.edu
Zi-Hua Lu
Alexander G Obukhov
Martha C Nowycky
Robert W Ledeen
Rutgers New Jersey Medical SchoolRutgers, The State University of New Jersey · US

Funding

Role of Nuclear Gangliosides in Neuronal FunctionR01NS033912 · NINDS · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI LEDEEN, ROBERT W · 1996 to 2012
$3.8M
REGULATION OF EXCITATION-SECRETION COUPLING MECHANISMSR01NS040167 · NINDS · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI NOWYCKY, MARTHA C · 1999 to 2002
$698k
NINDS NIH HHS NS033912NINDS NIH HHS NS040167NINDS NIH HHS R01 NS033912
6 · The paper itself

Abstract

Previous studies demonstrated that cross-linking of GM1 ganglioside with multivalent ligands, such as B subunit of cholera toxin (CtxB), induced Ca2+ influx through an unidentified, voltage-independent channel in several cell types. Application of CtxB to undifferentiated NG108-15 cells resulted in outgrowth of axon-like neurites in a Ca2+ influx-dependent manner. In this study, we demonstrate that CtxB-induced Ca2+ influx is mediated by TRPC5 channels, naturally expressed in these cells and primary neurons. Both Ca2+ influx and neurite induction were blocked by TRPC5 small interfering RNA (siRNA). Pretreatment of NG108-15 cells with neuraminidase increased cell-surface GM1 and greatly enhanced the signal. GM1 was not directly associated with TRPC5 but rather with alpha5beta1 integrin, which opened the channel through a signaling sequence after cross-linking of the GM1/integrin complex. This cascade included autophosphorylation of focal adhesion kinase and subsequent activation of phospholipase Cgamma (PLCgamma) and phosphoinositide-3 kinase [PI(3)K]. Pharmacological blockers that inhibited tyrosine kinase, PLC, and PI(3)K suppressed both CtxB-induced Ca2+ influx and neurite outgrowth. These were also suppressed by SK&F96365, a nonspecific transient receptor potential channel blocker. Confocal immunocytochemistry revealed that GM1 cross-linking induced colocalization of GM1 with these signaling elements in sprouting regions of plasma membrane. In primary cerebellar granular neurons (CGNs), TRPC5 was detected at 2 d in vitro (2 DIV), a stage corresponding to CtxB-stimulated Ca2+ influx. Neurite outgrowth in CGNs, determined at 3 DIV, was accelerated by CtxB and suppressed by TRPC5 siRNA and the above blockers. The crucial role of GM1 was indicated with CGNs from ganglio-series null mice, in which growth of axons was significantly retarded.

Indexed as

Integrin alpha5beta1AnimalsAxonsCalciumCell MembraneCells, CulturedCerebellumCholera ToxinCross-Linking ReagentsEnzyme ActivationFocal Adhesion Protein-Tyrosine KinasesG(M1) GangliosideIntegrinsMiceMice, KnockoutNeuritesCalciumCholera ToxinCross-Linking ReagentsFocal Adhesion Protein-Tyrosine KinasesG(M1) GangliosideIntegrin alpha5beta1IntegrinsPhosphatidylinositol 3-KinasesPhospholipase C gammaTrpc5 protein, mouseTRPC Cation Channels

Identifiers

PMID17626205
PMCPMC6672619
OpenAlexW2039129408

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.