PXD033751

PXD033751 is an original dataset announced via ProteomeXchange.

Title	Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity
Description	Gephyrin (GPHN) regulates the clustering of postsynaptic components at inhibitory synapses and is involved in pathophysiology of neuropsychiatric disorders. Here, we uncover an extensive diversity of GPHN transcripts that are tightly controlled by splicing during mouse and human brain development. Proteomic analysis reveals at least a hundred isoforms of GPHN incorporated at inhibitory Glycine and gamma-aminobutyric acid A receptors containing synapses. They exhibit different localization and postsynaptic clustering properties, and altering the expression level of one isoform is sufficient to affect the number, size, and density of inhibitory synapses in cerebellar Purkinje cells. Furthermore, we discovered that splicing defectsreported in neuropsychiatric disorders are carried by multiple alternative GPHN transcripts, demonstrating the need for a thorough analysis of the GPHN transcriptome in patients. Overall, we show that alternative splicing of GPHN is an important genetic variation to consider in neurological diseases and a determinant of the diversity of postsynaptic inhibitory synapses.
HostingRepository	PRIDE
AnnounceDate	2022-06-28
AnnouncementXML	Submission_2022-06-28_00:00:40.296.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Schlosser
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-06 10:46:23	ID requested
⏵ 1	2022-06-28 00:00:41	announced

Dos Reis R, Kornobis E, Pereira A, Tores F, Carrasco J, Gautier C, Jahannault-Talignani C, Nitschk, é P, Muchardt C, Schlosser A, Maric HM, Ango F, Allemand E, Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity. Nat Commun, 13(1):3507(2022) [pubmed]

submitter keyword: Gephyrin, splice variants, inhibitory synapses

Andreas Schlosser
contact affiliation	Rudolf-Virchow-Zentrum Center for Integrative and Translational Bioimaging Universität Würzburg Josef-Schneider-Str. 2 97080 Würzburg
contact email	andreas.schlosser@virchow.uni-wuerzburg.de
lab head
Andreas Schlosser
contact affiliation	Mass Spectrometry and Proteomics
contact email	andreas.schlosser@virchow.uni-wuerzburg.de
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/PXD033751

PRIDE project URI

• PRIDE
  1. PXD033751
     1. Label: PRIDE project
     2. Name: Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity