ArticleProceedings of the National Academy of Sciences of the United States of America2016
A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- Late development of OCD-like phenotypes in Dlgap1 knockout mice.Psychopharmacology · 2025Article
- Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans.Molecular psychiatry · 2024Article
- nArgBP2 together with GKAP and SHANK3 forms a dynamic layered structure.Frontiers in cellular neuroscience · 2024Article
- Phosphorylation-dependent recognition of diverse protein targets by the cryptic GK domain of MAGI MAGUKs.Science advances · 2023Article
- Review
- Physical Activity, Gut Microbiota, and Genetic Background for Children and Adolescents with Autism Spectrum Disorder.Children (Basel, Switzerland) · 2022Review
- IRSp53 promotes postsynaptic density formation and actin filament bundling.The Journal of cell biology · 2022Article
- Phosphoproteome Analysis Identifies a Synaptotagmin-1-Associated Complex Involved in Ischemic Neuron Injury.Molecular & cellular proteomics : MCP · 2022Article
- Resonance assignment of the Shank1 PDZ domain.Biomolecular NMR assignments · 2022Article
- Neuroligin-3 and neuroligin-4X form nanoscopic clusters and regulate growth cone organization and size.Human molecular genetics · 2022Article
- Bidirectional protein-protein interactions control liquid-liquid phase separation of PSD-95 and its interaction partners.iScience · 2022Article
- Proteomic insights into synaptic signaling in the brain: the past, present and future.Molecular brain · 2021Review
- Integrated analysis of Shank1 PDZ interactions with C-terminal and internal binding motifs.Current research in structural biology · 2021Article
- CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation.Cell research · 2021Article
- MotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity.Protein science : a publication of the Protein Society · 2019Article
- Phase Separation-Mediated TARP/MAGUK Complex Condensation and AMPA Receptor Synaptic Transmission.Neuron · 2019Article
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Molecular Dynamics Simulations of Wild Type and Mutants of SAPAP in Complexed with Shank3.International journal of molecular sciences · 2019Article
- International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature.Pharmacological reviews · 2018Review
Corrections and comments
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Authors and funding
7 authors.
Funding
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Abstract
Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ-binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders.
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