ArticlePLoS biology2018
An opposing function of paralogs in balancing developmental synapse maturation.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- PSD-95 drives binocular vision maturation critical for predation.bioRxiv : the preprint server for biology · 2026Article
- The synaptic vesicle cluster as a controller of pre- and postsynaptic structure and function.The Journal of physiology · 2025Review
- Distinct transmission sites within a synapse for strengthening and homeostasis.Science advances · 2025Article
- Input-Specific Localization of NMDA Receptor GluN2 Subunits in Thalamocortical Neurons.Journal of neurochemistry · 2025Article
- A synapse-specific refractory period for plasticity at individual dendritic spines.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A synapse-specific refractory period for plasticity at individual dendritic spines.bioRxiv : the preprint server for biology · 2024Article
- A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder.Genes, brain, and behavior · 2023Article
- Defects in early synaptic formation and neuronal function in Prader-Willi syndrome.Scientific reports · 2023Article
- Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model.Molecular autism · 2023Article
- Article
- Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Analysis of Huntington's Disease Modifiers Using the Hyperbolic Mapping of the Protein Interaction Network.International journal of molecular sciences · 2022Article
- Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability.Molecular psychiatry · 2022Article
- Selective behavioural impairments in mice heterozygous for the cross disorder psychiatric risk gene DLG2.Genes, brain, and behavior · 2022Article
- Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder.Genes, brain, and behavior · 2022Article
- A Deficiency of the Psychiatric Risk Gene DLG2/PSD-93 Causes Excitatory Synaptic Deficits in the Dorsolateral Striatum.Frontiers in molecular neuroscience · 2022Article
- The impact of SBF2 on taxane-induced peripheral neuropathy.PLoS genetics · 2022Article
- Silent Synapses in Cocaine-Associated Memory and Beyond.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Spine dynamics of PSD-95-deficient neurons in the visual cortex link silent synapses to structural cortical plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- AMPA and NMDA Receptor Trafficking at Cocaine-Generated Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The disc-large (DLG)-membrane-associated guanylate kinase (MAGUK) family of proteins forms a central signaling hub of the glutamate receptor complex. Among this family, some proteins regulate developmental maturation of glutamatergic synapses, a process vulnerable to aberrations, which may lead to neurodevelopmental disorders. As is typical for paralogs, the DLG-MAGUK proteins postsynaptic density (PSD)-95 and PSD-93 share similar functional domains and were previously thought to regulate glutamatergic synapses similarly. Here, we show that they play opposing roles in glutamatergic synapse maturation. Specifically, PSD-95 promoted, whereas PSD-93 inhibited maturation of immature α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptor (AMPAR)-silent synapses in mouse cortex during development. Furthermore, through experience-dependent regulation of its protein levels, PSD-93 directly inhibited PSD-95's promoting effect on silent synapse maturation in the visual cortex. The concerted function of these two paralogs governed the critical period of juvenile ocular dominance plasticity (jODP), and fine-tuned visual perception during development. In contrast to the silent synapse-based mechanism of adjusting visual perception, visual acuity improved by different mechanisms. Thus, by controlling the pace of silent synapse maturation, the opposing but properly balanced actions of PSD-93 and PSD-95 are essential for fine-tuning cortical networks for receptive field integration during developmental critical periods, and imply aberrations in either direction of this process as potential causes for neurodevelopmental disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.