Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
PTPδ, encoded by PTPRD, is implicated in various neurological, psychiatric, and neurodevelopmental disorders, but the underlying mechanisms remain unclear. PTPδ trans-synaptically interacts with multiple postsynaptic adhesion molecules, which involves its extracellular alternatively spliced mini-exons, meA and meB. While PTPδ-meA functions have been studied in vivo, PTPδ-meB has not been studied. Here, we report that, unlike homozygous PTPδ-meA-mutant mice, homozygous PTPδ-meB-mutant (Ptprd-meB) mice show markedly reduced early postnatal survival. Heterozygous Ptprd-meB male mice show behavioral abnormalities and decreased excitatory synaptic density and transmission in dentate gyrus granule cells (DG-GCs). Proteomic analyses identify decreased postsynaptic density levels of IL1RAP, a known trans-synaptic partner of meB-containing PTPδ. Accordingly, IL1RAP-mutant mice show decreased excitatory synaptic transmission in DG-GCs. Ptprd-meB DG interneurons with minimal IL1RAP expression show increased excitatory synaptic density and transmission. Therefore, PTPδ-meB is important for survival, synaptic, and behavioral phenotypes and regulates excitatory synapses in cell-type-specific and IL1RAP-dependent manners.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075705 | PMC |
| http://dx.doi.org/10.1038/s41467-025-59685-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ABCA7 variants impact phosphatidylcholine and mitochondria in neurons.
Nature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFGluN2A-NMDA receptor inhibition disinhibits the prefrontal cortex, reduces forced swim immobility, and impairs sensorimotor gating.
Acta Pharmacol Sin
September 2025
Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Bas
Recent investigations into the rapid antidepressant effects of ketamine, along with studies on schizophrenia-related susceptibility genes, have highlighted the GluN2A subunit as a critical regulator of both emotion and cognition. However, the specific impacts of acute pharmacological inhibition of GluN2A-containing NMDA receptors on brain microcircuits and the subsequent behavioral consequences remain poorly understood. In this study, we first examined the effects of MPX-004, a selective GluN2A NMDA receptor inhibitor, on behavior within the dorsomedial prefrontal cortex (dmPFC).
View Article and Find Full Text PDFDentate granule cell capacitance is stable across the light-dark cycle.
eNeuro
September 2025
Department of Neurobiology and McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL35294 and.
The plasma membrane acts as a capacitor that plays a critical role in neuronal excitability and signal propagation. Neuronal capacitance is proportional to the area of the cell membrane, thus is often used as a measure of cell size that is assumed to be relatively stable. Recent work proposes that the capacitance of dentate granule cells and cortical pyramidal cells changes across the light-dark cycle in a manner that alters synaptic integration.
View Article and Find Full Text PDFTrans-synaptic interaction with mGluR6 contributes to ELFN1 presynaptic enrichment in rod photoreceptors.
J Neurosci
September 2025
Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada, B3H4R2
At the glutamatergic synapses between rod photoreceptors and ON-type bipolar cells, neurotransmitter is detected by the postsynaptic metabotropic glutamate receptor mGluR6. This receptor forms trans-synaptic interactions with ELFN1, a presynaptic cell adhesion molecule expressed in rods, and ELFN1 is important for mGluR6 localization at bipolar cell dendritic tips. Here, we show that in mice of either sex lacking mGluR6, the presynaptic localization of ELFN1 is disrupted.
View Article and Find Full Text PDFUBQLN4 regulates seizures by promoting the proteasomal degradation of GluN2B.
Neurobiol Dis
September 2025
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing Key Laboratory of Neurology, Chongqing, China. Electronic address:
Ubiquilin 4 (UBQLN4) is an important molecule that regulates protein degradation through the ubiquitin-proteasome pathway. This study found that UBQLN4 expression is significantly reduced in a chronic epilepsy mouse model induced by kainic acid, primarily localized in neurons and widely distributed at excitatory post-synapses. Experiments involving adeno-associated virus-mediated overexpression or knockdown of UBQLN4 indicate that a reduction in UBQLN4 increases susceptibility to and severity of epilepsy, while its overexpression has a protective effect.
View Article and Find Full Text PDF