ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 151 citations in OpenAlex.
- The schizophrenia associated protein DISC1 forms a multivalent tetrameric hub via conserved UVR dimers.Nature communications · 2026Article
- PDE4B Missense Variant Increases Susceptibility to Post-traumatic Stress Disorder-Relevant Phenotypes in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- TransgenicCurrent issues in molecular biology · 2024Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Article
- Baicalin attenuates amyloid β oligomers induced memory deficits and mitochondria fragmentation through regulation of PDE-PKA-Drp1 signalling.Psychopharmacology · 2022Article
- Conformational heterogeneity coupled with β-fibril formation of a scaffold protein involved in chronic mental illnesses.Translational psychiatry · 2021Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Review
- Adolescent psychosocial stress enhances sensitization to cocaine exposure in genetically vulnerable mice.Neuroscience research · 2020Article
- Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits.Frontiers in neuroanatomy · 2020Article
- A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling.Translational psychiatry · 2019Article
- Article
- The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions.Journal of biomedical science · 2018Review
- Mechanisms underlying the role of DISC1 in synaptic plasticity.The Journal of physiology · 2018Review
- Altered phosphorylation, electrophysiology, and behavior on attenuation of PDE4B action in hippocampus.BMC neuroscience · 2017Article
- A structural organization for the Disrupted in Schizophrenia 1 protein, identified by high-throughput screening, reveals distinctly folded regions, which are bisected by mental illness-related mutations.The Journal of biological chemistry · 2017Article
- Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington's disease.The Journal of clinical investigation · 2017Article
- Identification of a multifunctional docking site on the catalytic unit of phosphodiesterase-4 (PDE4) that is utilised by multiple interaction partners.The Biochemical journal · 2017Article
- Primary Cilia as a Possible Link between Left-Right Asymmetry and Neurodevelopmental Diseases.Genes · 2017Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology.
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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.