ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.Antioxidants (Basel, Switzerland) · 2022Review
- A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline.Signal transduction and targeted therapy · 2021Article
- Molecular Mechanisms of Non-ionotropic NMDA Receptor Signaling in Dendritic Spine Shrinkage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Tau binding protein CAPON induces tau aggregation and neurodegeneration.Nature communications · 2019Article
- Neuronal nitric oxide synthase and affective disorders.IBRO reports · 2018Review
- Spatial quantification of the synaptic activity phenotype across large populations of neurons with Markov random fields.Bioinformatics (Oxford, England) · 2018Article
- Disruption of nNOS-NOS1AP protein-protein interactions suppresses neuropathic pain in mice.Pain · 2018Article
- NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2017Article
- A simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs.Nature communications · 2017Article
- DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD.Clinical epigenetics · 2017Article
- Efficient Binding of the NOS1AP C-Terminus to the nNOS PDZ Pocket Requires the Concerted Action of the PDZ Ligand Motif, the Internal ExF Site and Structural Integrity of an Independent Element.Frontiers in molecular neuroscience · 2017Article
- Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway.International journal of molecular sciences · 2016Article
- Insights into the C-terminal Peptide Binding Specificity of the PDZ Domain of Neuronal Nitric-oxide Synthase: CHARACTERIZATION OF THE INTERACTION WITH THE TIGHT JUNCTION PROTEIN CLAUDIN-3.The Journal of biological chemistry · 2016Article
- Overexpression of Isoforms of Nitric Oxide Synthase 1 Adaptor Protein, Encoded by a Risk Gene for Schizophrenia, Alters Actin Dynamics and Synaptic Function.Frontiers in cellular neuroscience · 2016Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity.
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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.