PXD023809

PXD023809 is an original dataset announced via ProteomeXchange.

Title	Reduced mGluR5 activity modulates mitochondrial function in the synapse
Description	The metabotropic glutamate receptor 5 (mGluR5) is a G-protein coupled receptor with an important role in synaptic function at multiple levels. In physiological conditions, mGluR5 is an essential modulator of synaptic plasticity, learning and memory; whereas in pathological conditions, it is an acknowledged therapeutic target that has been implicated in multiple brain disorders. However, the underlying mechanisms by which mGluR5 acts in these diverse synaptic functions and processes is only partly understood. In this study, we dissected the molecular synaptic modulation mediated by mGluR5 using genetic and pharmacological mouse models to chronically and acutely reduce mGluR5 activity. Using SWATH proteomic analysis, we found that next to dysregulation of synaptic proteins, the major regulation in protein expression in both models concerned specific processes in mitochondria, such as oxidative phosphorylation. Second, we observed morphological alterations in shape and area of specifically postsynaptic mitochondria in mGluR5 KO synapses using electron microscopy. Third, computational and biochemical assays suggested an increase of mitochondrial function in neurons, with increased level of NADP/H and oxidative damage in mGluR5 KO. Altogether, our observations provide diverse lines of evidence of the modulation of synaptic mitochondrial function by mGluR5. This connection suggests a role for mGluR5 as a mediator between synaptic activity and mitochondrial function, a finding which might be a relevant for the improvement of the clinical potential of mGluR5.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:51:57.651.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel A. Gonzalez-Lozano
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	L-cysteine methyl disulfide
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-25 23:01:59	ID requested
1	2021-08-27 06:22:00	announced
⏵ 2	2023-11-14 08:51:58	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Mitochondria, DIA, SWATH, Brain, Metabotropic glutamate receptor 5, Synapse, Mass spectrometry, Mice,mGluR5, CTEP

Ka Wan Li
contact affiliation	Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, The Netherlands
contact email	k.w.li@vu.nl
lab head
Miguel A. Gonzalez-Lozano
contact affiliation	Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam
contact email	m.a.gonzalezlozano@vu.nl
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/2021/08/PXD023809

PRIDE project URI

• PRIDE
  1. PXD023809
     1. Label: PRIDE project
     2. Name: Reduced mGluR5 activity modulates mitochondrial function in the synapse