ArticlePloS one2014
α-Actinin-2 mediates spine morphology and assembly of the post-synaptic density in hippocampal neurons.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
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- Evaluating Chronic Sex-Specific Changes in Glutamatergic Signaling Markers Following Traumatic Brain Injury.International journal of molecular sciences · 2026Article
- Regulation of NMDA receptor interactions with the actin cytoskeleton in dendritic spine development.Frontiers in cellular neuroscience · 2026Review
- Biological properties of α-actinin-2 and its role and mechanisms in disease development.Frontiers in physiology · 2026Review
- Widely Used CaMKII Regulatory Segment Mutations Cause Tight Actinin Binding and Dendritic Spine Enlargement in Unstimulated Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Modulation of SNARE-dependent exocytosis in astrocytes improves neuropathology in Huntington's disease.Disease models & mechanisms · 2024Article
- The Role of Acid-Sensing Ion Channel 1A (ASIC1A) in the Behavioral and Synaptic Effects of Oxycodone and Other Opioids.International journal of molecular sciences · 2024Article
- Cannabinerol (CBNR) Influences Synaptic Genes Associated with Cytoskeleton and Ion Channels in NSC-34 Cell Line: A Transcriptomic Study.Biomedicines · 2024Article
- Molecular basis of interactions between CaMKII and α-actinin-2 that underlie dendritic spine enlargement.eLife · 2023Article
- Induction of filopodia formation by α-Actinin-2 via RelA with a feedforward activation loop promoting overt bone marrow metastasis of gastric cancer.Journal of translational medicine · 2023Article
- The role of dendritic spines in epileptogenesis.Frontiers in cellular neuroscience · 2023Review
- Unraveling the mysteries of dendritic spine dynamics: Five key principles shaping memory and cognition.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2023Article
- Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus.Frontiers in neuroscience · 2022Article
- Age-related mitochondrial alterations in brain and skeletal muscle of the YAC128 model of Huntington disease.NPJ aging and mechanisms of disease · 2021Article
- Role of actin cytoskeleton in the organization and function of ionotropic glutamate receptors.Current research in structural biology · 2021Review
- A Human Induced Pluripotent Stem Cell-Derived Isogenic Model of Huntington's Disease Based on Neuronal Cells Has Several Relevant Phenotypic Abnormalities.Journal of personalized medicine · 2020Article
- Traceable stimulus-dependent rapid molecular changes in dendritic spines in the brain.Scientific reports · 2020Article
- Granule Cell Ensembles in Mouse Dentate Gyrus Rapidly Upregulate the Plasticity-Related Protein Synaptopodin after Exploration Behavior.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- Dendritic Spines in Alzheimer's Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure.International journal of molecular sciences · 2020Review
- Structural and functional features of medium spiny neurons in the BACHDΔN17 mouse model of Huntington's Disease.PloS one · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Dendritic spines are micron-sized protrusions that constitute the primary post-synaptic sites of excitatory neurotransmission in the brain. Spines mature from a filopodia-like protrusion into a mushroom-shaped morphology with a post-synaptic density (PSD) at its tip. Modulation of the actin cytoskeleton drives these morphological changes as well as the spine dynamics that underlie learning and memory. Several PSD molecules respond to glutamate receptor activation and relay signals to the underlying actin cytoskeleton to regulate the structural changes in spine and PSD morphology. α-Actinin-2 is an actin filament cross-linker, which localizes to dendritic spines, enriched within the post-synaptic density, and implicated in actin organization. We show that loss of α-actinin-2 in rat hippocampal neurons creates an increased density of immature, filopodia-like protrusions that fail to mature into a mushroom-shaped spine during development. α-Actinin-2 knockdown also prevents the recruitment and stabilization of the PSD in the spine, resulting in failure of synapse formation, and an inability to structurally respond to chemical stimulation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. The Ca2+-insensitive EF-hand motif in α-actinin-2 is necessary for the molecule's function in regulating spine morphology and PSD assembly, since exchanging it for the similar but Ca2+-sensitive domain from α-actinin-4, another α-actinin isoform, inhibits its function. Furthermore, when the Ca2+-insensitive domain from α-actinin-2 is inserted into α-actinin-4 and expressed in neurons, it creates mature spines. These observations support a model whereby α-actinin-2, partially through its Ca2+-insensitive EF-hand motif, nucleates PSD formation via F-actin organization and modulates spine maturation to mediate synaptogenesis.
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