ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review.Journal of psychiatry & neuroscience : JPN · 2018Pooled it
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- The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders.Protein & cell · 2022Review
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- Role of actin cytoskeleton in the organization and function of ionotropic glutamate receptors.Current research in structural biology · 2021Review
- A NovelMolecular syndromology · 2020Article
- AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.Cellular and molecular life sciences : CMLS · 2019Review
- Temporal Regulation of Dendritic Spines Through NrCAM-Semaphorin3F Receptor Signaling in Developing Cortical Pyramidal Neurons.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Rapid homeostatic downregulation of LTP by extrasynaptic GluN2B receptors.Journal of neurophysiology · 2018Article
- EphBs and ephrin-Bs: Trans-synaptic organizers of synapse development and function.Molecular and cellular neurosciences · 2018Review
- Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice of various ages.Journal of anatomy · 2018Article
- The transcription factor XBP1s restores hippocampal synaptic plasticity and memory by control of the Kalirin-7 pathway in Alzheimer model.Molecular psychiatry · 2017Article
- Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder.Journal of autism and developmental disorders · 2017Article
- Protracted and asynchronous accumulation of PSD95-family MAGUKs during maturation of nascent dendritic spines.Developmental neurobiology · 2017Article
- MAGUKs: multifaceted synaptic organizers.Current opinion in neurobiology · 2017Review
- The transcription factor XBP1 in memory and cognition: Implications in Alzheimer disease.Molecular medicine (Cambridge, Mass.) · 2017Article
- NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of NR2B.Scientific reports · 2016Article
- A non-coding variant in the 5' UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disability.European journal of human genetics : EJHG · 2016Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Membrane-associated guanylate kinases (MAGUKs), including SAP102, PSD-95, PSD-93, and SAP97, are scaffolding proteins for ionotropic glutamate receptors at excitatory synapses. MAGUKs play critical roles in synaptic plasticity; however, details of signaling roles for each MAGUK remain largely unknown. Here we report that SAP102 regulates cortical synapse development through the EphB and PAK signaling pathways. Using lentivirus-delivered shRNAs, we found that SAP102 and PSD-95, but not PSD-93, are necessary for excitatory synapse formation and synaptic AMPA receptor (AMPAR) localization in developing mouse cortical neurons. SAP102 knockdown (KD) increased numbers of elongated dendritic filopodia, which is often observed in mouse models and human patients with mental retardation. Further analysis revealed that SAP102 coimmunoprecipitated the receptor tyrosine kinase EphB2 and RacGEF Kalirin-7 in neonatal cortex, and SAP102 KD reduced surface expression and dendritic localization of EphB. Moreover, SAP102 KD prevented reorganization of actin filaments, synapse formation, and synaptic AMPAR trafficking in response to EphB activation triggered by its ligand ephrinB. Last, p21-activated kinases (PAKs) were downregulated in SAP102 KD neurons. These results demonstrate that SAP102 has unique roles in cortical synapse development by mediating EphB and its downstream PAK signaling pathway. Both SAP102 and PAKs are associated with X-linked mental retardation in humans; thus, synapse formation mediated by EphB/SAP102/PAK signaling in the early postnatal brain may be crucial for cognitive development.
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Registered trials
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.