PXD050810

PXD050810 is an original dataset announced via ProteomeXchange.

Title	MDGA2 constrains the BDNF/TrkB signaling
Description	MDGA2 is an excitatory synaptic suppressor and its mutations have been associated with autism spectrum disorder (ASD). However, the detailed physiological function of MDGA2 and the mechanism underlying MDGA2 deficiency-caused ASD has yet to be elucidated. Herein, we not only confirm that Mdga2+/- mice exhibit increased excitatory synapse transmission and ASD-like behaviors, but also identify aberrant BDNF/TrkB signaling activation in these mice. We demonstrate that MDGA2 interacts with TrkB through its MAM domain, thereby competing the binding of BDNF to TrkB. Both loss of MDGA2 and the ASD-associated MDGA2 V930I mutation promote the BDNF/TrkB signaling activity. Importantly, we demonstrate that inhibiting the BDNF/TrkB signaling by both small molecular compound and MDGA2-derived peptide can attenuate the increase of AMPA receptor-mediated excitatory synaptic activity and social deficits in MDGA2 deficient mice. These results highlight a novel MDGA2-BDNF/TrkB-dependent mechanism underlying the synaptic function regulation, which may become a therapeutic target for ASD.
HostingRepository	PRIDE
AnnounceDate	2025-02-06
AnnouncementXML	Submission_2025-02-05_18:53:14.505.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	dongdong zhao
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	2024-03-20 05:58:33	ID requested
⏵ 1	2025-02-05 18:53:14	announced

Dataset with its publication pending

submitter keyword: ASD, MDGA2, BDNF, TrkB

dong dong zhao
contact affiliation	Medical College of Xiamen University
contact email	19871230zdd@163.com
lab head
dongdong zhao
contact affiliation	Xiamen University
contact email	19871230zdd@163.com
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/2025/02/PXD050810

PRIDE project URI

• PRIDE
  1. PXD050810
     1. Label: PRIDE project
     2. Name: MDGA2 constrains the BDNF/TrkB signaling