Evidence map›Paper›PMID 30822303›Full record

ArticlePLoS biology2019

The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation.

Kasper Engholm-Keller, Ashley J Waardenberg, Johannes A Müller, Jesse R Wark, Rowena N Fernando, Jonathan W Arthur, Phillip J Robinson, Dirk Dietrich, Susanne Schoch, Mark E Graham

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 51 citations in OpenAlex.

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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

10 authors at 2 institutions in 3 countries.

Kasper Engholm-KellerSynapse Proteomics, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.ORCID 0000-0001-5988-2632
Ashley J WaardenbergBioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.ORCID 0000-0002-9382-7490
Johannes A MüllerInstitute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
Jesse R WarkSynapse Proteomics, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.
Rowena N FernandoSynapse Proteomics, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.
Jonathan W ArthurBioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.ORCID 0000-0003-3615-7352
Phillip J RobinsonCell Signalling Unit, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.ORCID 0000-0002-7878-0313
Dirk DietrichDepartment of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
Susanne SchochInstitute of Neuropathology, University of Bonn Medical Center, Bonn, Germany.ORCID 0000-0002-2046-2670
Mark E GrahamSynapse Proteomics, Children's Medical Research Institute, The University of Sydney, Westmead, Australia.ORCID 0000-0002-7290-1217
The University of Sydney · AUUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Depolarization of presynaptic terminals stimulates calcium influx, which evokes neurotransmitter release and activates phosphorylation-based signalling. Here, we present the first global temporal profile of presynaptic activity-dependent phospho-signalling, which includes two KCl stimulation levels and analysis of the poststimulus period. We profiled 1,917 regulated phosphopeptides and bioinformatically identified six temporal patterns of co-regulated proteins. The presynaptic proteins with large changes in phospho-status were again prominently regulated in the analysis of 7,070 activity-dependent phosphopeptides from KCl-stimulated cultured hippocampal neurons. Active zone scaffold proteins showed a high level of activity-dependent phospho-regulation that far exceeded the response from postsynaptic density scaffold proteins. Accordingly, bassoon was identified as the major target of neuronal phospho-signalling. We developed a probabilistic computational method, KinSwing, which matched protein kinase substrate motifs to regulated phosphorylation sites to reveal underlying protein kinase activity. This approach allowed us to link protein kinases to profiles of co-regulated presynaptic protein networks. Ca2+- and calmodulin-dependent protein kinase IIα (CaMKIIα) responded rapidly, scaled with stimulus strength, and had long-lasting activity. Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) was the main protein kinase predicted to control a distinct and significant pattern of poststimulus up-regulation of phosphorylation. This work provides a unique resource of activity-dependent phosphorylation sites of synaptosomes and neurons, the vast majority of which have not been investigated with regard to their functional impact. This resource will enable detailed characterization of the phospho-regulated mechanisms impacting the plasticity of neurotransmitter release.

Indexed as

AnimalsCalciumCalmodulinCyclin-Dependent Kinase 5MaleMass SpectrometryPhosphoproteinsPhosphorylationPotassium ChloridePresynaptic TerminalsRatsRats, Sprague-DawleySignal TransductionSynaptosomesCalciumCalmodulinCyclin-Dependent Kinase 5PhosphoproteinsPotassium Chloride

Identifiers

PMID30822303
PMCPMC6415872
OpenAlexW2919962987

What Socratic holds

Textmetadata
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 Socratic graph.