PXD031379-1

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

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PRIDE project URI

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