MINT2/APBA2 is a synaptic adaptor protein involved in excitatory synaptic transmission. Several nonsynonymous coding variants in MINT2 have been identified in autism spectrum disorders (ASDs); however, these rare variants have not been examined functionally and the pathogenic mechanisms are unknown. Here, we examined the synaptic effects of rat Mint2 N723S mutation (equivalent to autism-linked human MINT2 N722S mutation) which targets a conserved asparagine residue in the second PDZ domain of Mint2 that binds to neurexin-1α (Nrxn1α), a presynaptic cell-adhesion protein implicated in ASDs. We show the N723S mutation impairs Nrxn1α stabilization and trafficking to the membrane while binding to Nrxn1α remains unaffected. Using time-lapse imaging in primary mouse neurons, we found that the N723S mutant had more immobile puncta at neuronal processes compared to Mint2 wild type. We therefore, reasoned that the N723S mutant may alter the co-transport of Nrxn1α at axonal processes to presynaptic terminals. Indeed, we found the N723S mutation affected Nrxn1α localization at presynaptic terminals which correlated with a decrease in Nrxn-mediated synaptogenesis and miniature event frequency in excitatory synapses. Together, our data reveal Mint2 N723S leads to neuronal dysfunction, in part due to alterations in Nrxn1α surface trafficking and synaptic function of Mint2.
Pubmed ID: 30988517 RIS Download
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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
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View all literature mentionsThis polyclonal targets Mint2 antibody produced in rabbit
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis monoclonal targets Synaptobrevin 2
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis monoclonal targets alpha-Tubulin (DM1A) Mouse mAb
View all literature mentionsThis monoclonal targets Neurofilament
View all literature mentionsThis polyclonal targets Neurexin 1
View all literature mentionsThis monoclonal targets alpha 1 Sodium Potassium ATPase antibody [464.6] - Plasma Membrane Marker
View all literature mentionsThis polyclonal targets Mint2 antibody produced in rabbit
View all literature mentionsThis polyclonal targets
View all literature mentionsThis monoclonal targets GM130
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsUser interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentions