PXD010007

PXD010007 is an original dataset announced via ProteomeXchange.

Title	The temporal profile of activity-dependent presynaptic phospho-signalling reveals long lasting patterns of post-stimulus regulation
Description	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 post-stimulus 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. CaMKIIα responded rapidly, scaled with stimulus strength and had long-lasting activity. MAPK/ERK was the main protein kinase predicted to control a distinct and significant pattern of post-stimulus 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.
HostingRepository	PRIDE
AnnounceDate	2019-01-28
AnnouncementXML	Submission_2019-03-28_13:47:05.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Graham
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-01 08:57:15	ID requested
1	2019-01-28 03:41:03	announced
⏵ 2	2019-03-28 13:47:06	announced	Updated publication reference for PubMed record(s): 30822303.

Engholm-Keller K, Waardenberg AJ, M, ü, ller JA, Wark JR, Fernando RN, Arthur JW, Robinson PJ, Dietrich D, Schoch S, Graham ME, The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation. PLoS Biol, 17(3):e3000170(2019) [pubmed]

curator keyword: Biological

submitter keyword: Phosphorylation, neuron, presynaptic, synaptosome, depolarization, post-stimulus, signalling, rat, phosphatase, PP1, kinase,

Mark E. Graham
contact affiliation	Synapse Proteomics Group, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia
contact email	mgraham@cmri.org.au
lab head
Mark Graham
contact affiliation	Cell Signalling
contact email	mgraham@cmri.org.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/01/PXD010007

PRIDE project URI

• PRIDE
  1. PXD010007
     1. Label: PRIDE project
     2. Name: The temporal profile of activity-dependent presynaptic phospho-signalling reveals long lasting patterns of post-stimulus regulation