Differential Regional Expression and Ultrastructural Localization of α-Actinin-2, a Putative NMDA Receptor-Anchoring Protein, in Rat Brain
Open accessAbstract
Fast chemical neurotransmission is dependent on ionotropic receptors that are concentrated and immobilized at specific postsynaptic sites. The mechanisms of receptor clustering and anchoring in neuronal synapses are poorly understood but presumably involve molecular linkage of membrane receptor proteins to the postsynaptic cytoskeleton. Recently the actin-binding protein α-actinin-2 was shown to bind directly to the NMDA receptor subunits NR1 and NR2B (Wyszynski et al., 1997), suggesting that α-actinin-2 may function to attach NMDA receptors to the actin cytoskeleton. Here we show that α-actinin-2 is localized specifically in glutamatergic synapses in cultured hippocampal neurons. By immunogold electron microscopy, α-actinin-2 is concentrated over the postsynaptic density (PSD) of numerous asymmetric synapses where it colocalizes with NR1 immunoreactivity. Thus α-actinin-2 is appropriately positioned at the ultrastructural level to function as a postsynaptic-anchoring protein for NMDA receptors. α-Actinin-2 is not, however, exclusively found at the PSD; immunogold labeling was also associated with filaments and the spine apparatus of dendritic spines and with microtubules in dendritic shafts. α-Actinin-2 showed marked differential regional expression in rat brain. For instance, the protein is expressed at much higher levels in dentate gyrus than in area CA1 of the hippocampus. This differential regional expression implies that glutamatergic synapses in various parts of the brain differ with respect to their α-actinin-2 content and thus, potentially, the extent of possible interaction between α-actinin-2 and the NMDA receptor.
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The location of recorded neurons in CA2 was confirmed after fixation and by staining for α-actinin 2.
“The location of the recorded neurons in CA2 was subsequently confirmed after fixation of the slice for 1 hour in 4% paraformaldehyde in phosphate buffer (PBS). We further confirmed the location in CA2 by staining the slice for α-actinin 2, a protein enriched in the CA2 area (Wyszynski et al., 1998)”
From Strong CA2 Pyramidal Neuron Synapses Define a Powerful Disynaptic Cortico-Hippocampal Loop (2010) · cites this paper as Wyszynski et al., 1998
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- Authors
- Wyszynski, M., Kharazia, V., Shanghvi, R., Rao, A., Beggs, A. H., Craig, A. M., Weinberg, R., & Sheng, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of North Carolina at Chapel Hill (US)
- University of Illinois Urbana-Champaign (US)
- Boston Children's Hospital (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-02-15
- Volume
- 18
- Issue
- 4
- Pages
- 1383-1392
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4301037431
- Cited by
- 168
- References
- 28
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 1 · 2021: 1 · 2020: 13 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 4
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Funders
- Howard Hughes Medical Institute
- Muscular Dystrophy Association
- National Institutes of Health (NS29879)
- National Cancer Institute (CA66268-02, F32CA066268)
- National Institute of Neurological Disorders and Stroke (NS 35050, R01NS035050, NS-29879)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044345)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- ACTN2, NMDA receptor, postsynaptic density, glutamatergic synapses, hippocampal neurons, dendritic spines, actin cytoskeleton, NR1 subunit, dentate gyrus, synaptic ultrastructure
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