PXD031932-1

PXD031932 is an original dataset announced via ProteomeXchange.

Title	Unbalanced protein expression contributes to pathology in Fragile X Syndrome
Description	Dysregulated protein synthesis is a core pathogenic mechanism in Fragile X Syndrome (FX). The mGluR Theory of FX predicts that pathological synaptic changes arise from the excessive translation of mRNAs downstream of mGlu1/5 activation. Here, we use a combination of CA1 pyramidal neuron-specific Translating Ribosome Affinity Purification and RNA-seq (TRAP-seq) and proteomics to identify the overtranslating mRNAs supporting exaggerated mGlu1/5 -induced long-term synaptic depression (mGluR-LTD) in the FX mouse model (Fmr1-/y). Our results identify a robust translation of ribosomal proteins (RPs) upon mGlu1/5 stimulation that coincides with a reduced translation of long mRNAs encoding synaptic proteins. These changes are mimicked and occluded in Fmr1-/y neurons. In addition, proteomics analyses identify increased degradation of multiple proteins at hippocampal synapses, many of which are underexpressed at steady-state.
HostingRepository	PRIDE
AnnounceDate	2022-08-16
AnnouncementXML	Submission_2022-08-16_02:43:57.376.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	2022-02-28 03:31:46	ID requested
⏵ 1	2022-08-16 02:43:58	announced
2	2024-10-22 05:39:14	announced	2024-10-22: Updated project metadata.

Seo SS, Louros SR, Anstey N, Gonzalez-Lozano MA, Harper CB, Verity NC, Dando O, Thomson SR, Darnell JC, Kind PC, Li KW, Osterweil EK, Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome. Nat Commun, 13(1):3236(2022) [pubmed]

submitter keyword: Fragile X, FMR1, mGluR5, ribosome, proteasome, SWATH, mouse, brain, hippocampus, synapse

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/2022/06/PXD031932

PRIDE project URI

• PRIDE
  1. PXD031932
     1. Label: PRIDE project
     2. Name: Unbalanced protein expression contributes to pathology in Fragile X Syndrome