PXD031379

PXD031379 is an original dataset announced via ProteomeXchange.

Title	Targeted proteoform mapping uncovers specific Neurexin-3 variants required for dendritic inhibition
Description	Diversification of cell adhesion molecules by alternative splicing is proposed to underlie molecular codes for neuronal wiring. Transcriptomic approaches mapped detailed cell type-specific mRNA splicing programs. However, it has been hard to probe synapse-specific localization and function of the resulting protein splice isoforms, or “proteoforms”, in vivo. We here apply a proteoform-centric workflow in mice to test synapse-specific functions of splice isoforms of the synaptic adhesion molecule Neurexin-3 (NRXN3). We uncover a major proteoform, NRXN3 AS5, that is highly expressed in GABAergic interneurons and dendrite-targeting GABAergic terminals. NRXN3 AS5 abundance significantly diverges from the distribution of the Nrxn3 mRNA and is gated by translation-repressive elements. Nrxn3 AS5 isoform deletion results in selective impairment of dendrite-targeting interneuron synapses in the dentate gyrus without affecting somatic inhibition or glutamatergic perforant-path synapses. This work establishes cell- and synapse-specific functions of a specific neurexin proteoform and highlights the importance of alternative splicing regulation for synapse specification.
HostingRepository	PRIDE
AnnounceDate	2022-02-11
AnnouncementXML	Submission_2022-02-11_08:17:05.025.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031379
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Schmidt
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-01 03:40:17	ID requested
⏵ 1	2022-02-11 08:17:05	announced

Dataset with its publication pending

submitter keyword: Neurexin-3, targeted MS, AP-MS

Alexander Schmidt
contact affiliation	University of Basel, Biozentrum, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
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/2022/02/PXD031379

PRIDE project URI

• PRIDE
  1. PXD031379
     1. Label: PRIDE project
     2. Name: Targeted proteoform mapping uncovers specific Neurexin-3 variants required for dendritic inhibition