Evidence map›Paper›PMID 10477751›Full record

ArticleThe Journal of cell biology1999

Depolarization and neurotrophins converge on the phosphatidylinositol 3-kinase-Akt pathway to synergistically regulate neuronal survival.

A R Vaillant, I Mazzoni, C Tudan, M Boudreau, D R Kaplan, F D Miller

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

Article in The Journal of cell biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% 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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 251 citations in OpenAlex.

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  11. αAmerican journal of physiology. Cell physiology · 2019
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19 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

A R VaillantCenter for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.
I Mazzoni
C Tudan
M Boudreau
D R Kaplan
F D Miller
Montreal Neurological Institute and Hospital · CAMcGill University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this report, we have examined the mechanisms whereby neurotrophins and neural activity coordinately regulate neuronal survival, focussing on sympathetic neurons, which require target-derived NGF and neural activity for survival during development. When sympathetic neurons were maintained in suboptimal concentrations of NGF, coincident depolarization with concentrations of KCl that on their own had no survival effect, synergistically enhanced survival. Biochemical analysis revealed that depolarization was sufficient to activate a Ras-phosphatidylinositol 3-kinase-Akt pathway (Ras-PI3-kinase-Akt), and function-blocking experiments using recombinant adenovirus indicated that this pathway was essential for approximately 50% of depolarization-mediated neuronal survival. At concentrations of NGF and KCl that promoted synergistic survival, these two stimuli converged to promote increased PI3-kinase-dependent Akt phosphorylation. This convergent PI3-kinase-Akt pathway was essential for synergistic survival. In contrast, inhibition of calcium/calmodulin-dependent protein kinase II revealed that, while this molecule was essential for depolarization-induced survival, it had no role in KCl- induced Akt phosphorylation, nor was it important for synergistic survival by NGF and KCl. Thus, NGF and depolarization together mediate survival of sympathetic neurons via intracellular convergence on a Ras-PI3-kinase-Akt pathway. This convergent regulation of Akt may provide a general mechanism for coordinating the effects of growth factors and neural activity on neuronal survival throughout the nervous system.

Indexed as

AnimalsAnimals, NewbornApoptosisCalcium-Calmodulin-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein Kinase Type 2Cells, CulturedCell SurvivalDrug SynergismEnzyme ActivationMembrane PotentialsMitogen-Activated Protein Kinase KinasesNerve Growth FactorsNeuronsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationAkt1 protein, ratCalcium-Calmodulin-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein Kinase Type 2Mitogen-Activated Protein Kinase KinasesNerve Growth FactorsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPotassium ChlorideProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Receptor Protein-Tyrosine KinasesReceptors, Nerve Growth FactorReceptor, trkA

Identifiers

PMID10477751
PMCPMC2169479
OpenAlexW2102410706

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.