ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
IQGAP1 regulates NR2A signaling, spine density, and cognitive processes.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 94 citations in OpenAlex.
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- Hippocampal ERK2 dimerization regulates inhibitory avoidance memory reconsolidation and synaptic plasticity.iScience · 2026Article
- The scaffold protein IQGAP1 regulates the epithelial NaThe Journal of biological chemistry · 2025Article
- Dragon's Blood Modulates Disulfidptosis-Related Genes to Alleviate Ischemic Brain Injury in Mice.Neurochemical research · 2025Article
- Review
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- Identification of disulfidptosis-related genes and subgroups in Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Genome-wide translation control analysis of developing human neurons.Molecular brain · 2022Article
- Grape-Seed-Derived Procyanidin Attenuates Chemotherapy-Induced Cognitive Impairment by Suppressing MMP-9 Activity and Related Blood-Brain-Barrier Damage.Brain sciences · 2022Article
- GluN2A-ERK-mTOR pathway confers a vulnerability to LPS-induced depressive-like behaviour.Behavioural brain research · 2022Article
- MiR-33-5p Regulates CREB to Induce Morphine State-dependent Memory in Rats: Interaction with the µ Opioid Receptor.International journal of molecular and cellular medicine · 2022Article
- MiR-124 Regulates IQGAP1 and Participates in the Relationship Between Morphine Dependence Susceptibility and Cognition.Frontiers in psychiatry · 2022Article
- Machine learning models identify ferroptosis-related genes as potential diagnostic biomarkers for Alzheimer's disease.Frontiers in aging neuroscience · 2022Article
- Contributions of extracellular-signal regulated kinase 1/2 activity to the memory trace.Frontiers in molecular neuroscience · 2022Review
- Transferrin-Pep63-liposomes accelerate the clearance of Aβ and rescue impaired synaptic plasticity in early Alzheimer's disease models.Cell death discovery · 2021Article
- Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory.Frontiers in neuroscience · 2021Article
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- GluT4: A central player in hippocampal memory and brain insulin resistance.Experimental neurology · 2020Review
- Ligand-dependent spatiotemporal signaling profiles of the μ-opioid receptor are controlled by distinct protein-interaction networks.The Journal of biological chemistry · 2019Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
General or brain-region-specific decreases in spine number or morphology accompany major neuropsychiatric disorders. It is unclear, however, whether changes in spine density are specific for an individual mental process or disorder and, if so, which molecules confer such specificity. Here we identify the scaffolding protein IQGAP1 as a key regulator of dendritic spine number with a specific role in cognitive but not emotional or motivational processes. We show that IQGAP1 is an important component of NMDAR multiprotein complexes and functionally interacts with the NR2A subunits and the extracellular signal-regulated kinase 1 (ERK1) and ERK2 signaling pathway. Mice lacking the IQGAP1 gene exhibited significantly lower levels of surface NR2A and impaired ERK activity compared to their wild-type littermates. Accordingly, primary hippocampal cultures of IQGAP1(-/-) neurons exhibited reduced surface expression of NR2A and disrupted ERK signaling in response to NR2A-dependent NMDAR stimulation. These molecular changes were accompanied by region-specific reductions of dendritic spine density in key brain areas involved in cognition, emotion, and motivation. IQGAP1 knock-outs exhibited marked long-term memory deficits accompanied by impaired hippocampal long-term potentiation (LTP) in a weak cellular learning model; in contrast, LTP was unaffected when induced with stronger stimulation paradigms. Anxiety- and depression-like behavior remained intact. On the basis of these findings, we propose that a dysfunctional IQGAP1 gene contributes to the cognitive deficits in brain disorders characterized by fewer dendritic spines.
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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.