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Integrins Control Dendritic Spine Plasticity in Hippocampal Neurons through NMDA Receptor and Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Actin Reorganization
Open accessAbstract
The formation of dendritic spines during development and their structural plasticity in the adult brain are critical aspects of synaptogenesis and synaptic plasticity. Many different factors and proteins have been shown to control dendritic spine development and remodeling (Ethell and Pasquale, 2005). The extracellular matrix (ECM) components and their cell surface receptors, integrins, have been found in the vicinity of synapses and shown to regulate synaptic efficacy and play an important role in long-term potentiation (Bahr et al., 1997; Chavis and Westbrook, 2001; Chan et al., 2003; Lin et al., 2003; Bernard-Trifilo et al., 2005). Although molecular mechanisms by which integrins affect synaptic efficacy have begun to emerge, their role in structural plasticity is poorly understood. Here, we show that integrins are involved in spine remodeling in cultured hippocampal neurons. The treatment of 14 d in vitro hippocampal neurons with arginine–glycine–aspartate (RGD)-containing peptide, an established integrin ligand, induced elongation of existing dendritic spines and promoted formation of new filopodia. These effects were also accompanied by integrin-dependent actin reorganization and synapse remodeling, which were partially inhibited by function-blocking antibodies against β1 and β3 integrins. This actin reorganization was blocked with the NMDA receptor (NMDAR) antagonist MK801 [(+)-5-methyl-10,11-dihydro-5 H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate]. The Ca 2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93 (N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide) also suppressed RGD-induced actin reorganization and synapse remodeling. Our findings show that integrins control ECM-mediated spine remodeling in hippocampal neurons through NMDAR/CaMKII-dependent actin reorganization.
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“spine development and reorganization by mediating interactions with the extracellular matrix and the dynamic reorganization of the intracellular cytoskeleton (Shi and Ethell 2006)”
From The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Shi and Ethell 2006
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Metadata
- Authors
- Shi, Y., & Ethell, I. M.
- Affiliations
- University of California, Riverside (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-02-08
- Volume
- 26
- Issue
- 6
- Pages
- 1813-1822
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6793632
- OpenAlex
- W2109129502
- Cited by
- 200
- References
- 68
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 3 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 9 · 2016: 16 · 2015: 9 · 2014: 10 · 2013: 10 · 2012: 15
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH067121, MH 67121)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- integrins, dendritic spine plasticity, hippocampal neurons, NMDA receptor, CaMKII, actin reorganization, extracellular matrix, RGD peptide, filopodia, synaptic remodeling, beta1 integrin, CD61, MK-801, KN-93
- MeSH terms
- Actins, Animals, Cells, Cultured, Dendrites, Hippocampus, Neuronal Plasticity, Neurons, Oligopeptides, Spinal Cord, Integrins, Receptors, N-Methyl-D-Aspartate, Calcium-Calmodulin-Dependent Protein Kinases, Mice
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