{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhao D"],"funding":["Postdoctoral Science Foundation of China","National Natural Science Foundation of China"],"pagination":["e3003047"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11960969"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(4)"],"pubmed_abstract":["Memprin/A5/mu (MAM) domain containing glycosylphosphatidylinositol anchor 2 (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 brain-derived neurotrophic factor/tyrosine kinase B (BDNF/TrkB) signaling activation in these mice. We demonstrate that MDGA2 interacts with TrkB through its memprin/A5/mu domain, thereby competing the binding of BDNF to TrkB. Both loss of MDGA2 and the ASD-associated MDGA2 V930I mutation promote the BDNF/TrkB signa"],"journal":["PLoS biology"],"pubmed_title":["Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice."],"pmcid":["PMC11960969"],"funding_grant_id":["2022M722651","U21A20361","82001442","2020M671948","82130039"],"pubmed_authors":["Jiang Y","Zheng N","Huo Y","Wang S","Zhang YW","Zhu X","Zhao D","Yang D","Zhou Y","Wu Y"],"additional_accession":[]},"is_claimable":false,"name":"Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice.","description":"Memprin/A5/mu (MAM) domain containing glycosylphosphatidylinositol anchor 2 (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 brain-derived neurotrophic factor/tyrosine kinase B (BDNF/TrkB) signaling activation in these mice. We demonstrate that MDGA2 interacts with TrkB through its memprin/A5/mu domain, thereby competing the binding of BDNF to TrkB. Both loss of MDGA2 and the ASD-associated MDGA2 V930I mutation promote the BDNF/TrkB signa","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-01T19:21:13.207Z","creation":"2025-06-26T03:06:08.004Z"},"accession":"S-EPMC11960969","cross_references":{"pubmed":["40168357"],"doi":["10.1371/journal.pbio.3003047"]}}