Actin Out: Regulation of the Synaptic Cytoskeleton
Open accessAbstract
The small size of dendritic spines belies the elaborate role they play in excitatory synaptic transmission and ultimately complex behaviors. The cytoskeletal architecture of the spine is predominately composed of actin filaments. These filaments, which at first glance might appear simple, are also surprisingly complex. They dynamically assemble into different structures and serve as a platform for orchestrating the elaborate responses of the spine during spinogenesis and experience-dependent plasticity. Multiple mutations associated with human neurodevelopmental and psychiatric disorders involve genes that encode regulators of the synaptic cytoskeleton. A major, unresolved question is how the disruption of specific actin filament structures leads to the onset and progression of complex synaptic and behavioral phenotypes. This review will cover established and emerging mechanisms of actin cytoskeletal remodeling and how this influences specific aspects of spine biology that are implicated in disease.
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The FA pathway can modulate F-actin dynamics through regulating multiple actin-binding proteins and controls the shape of the dendritic spine.
“Among numerous biological functions, the FA pathway can modulate F-actin dynamics through regulating multiple actin-binding proteins, e.g., cortactin, profilin, drebrin or cofilin, and controls the shape of the dendritic spine [125].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [125]
The Dendritic Spine Actin Regulators and Actin Filament Assembly sections describe proteins that regulate F-actin dynamics and affect spine morphology; the copy also discusses cortactin and cofilin. It does not identify these effects as those of an “FA pathway” or support drebrin as one of the listed examples. Page numbers are unavailable in our copy. (LLM, conf=0.82)
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Nakano-Kobayashi, A., Tai, Y., Kasri, N. N., & Aelst, L. V. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0894-14.2014 · Cited by 31 · see citing works
Afadin Is Required for Maintenance of Dendritic Structure and Excitatory Tone
Srivastava, D. P., Copits, B. A., Xie, Z., Huda, R., Jones, K. A., Mukherji, S., Cahill, M. E., VanLeeuwen, J., Woolfrey, K. M., Rafalovich, I., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.363358 · Cited by 30 · see citing works
Ultrastructural abnormalities in CA1 hippocampus caused by deletion of the actin regulator WAVE-1
Hazai, D., Szudoczki, R., Ding, J., Soderling, S. H., Weinberg, R. J., Sótonyi, P., & Rácz, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075248 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Kim, I. H., Wang, H., Soderling, S. H., and Yasuda, R. (2014) Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall. eLife 3, e02839 92. Soderling, S. H., Langeberg, L. K., Soderling, J. A., Davee, S. M., Simerly, R., Raber, J., and Scott, J. D. (2003) Loss of WAVE-1 causes sensorimotor retardation and reduced learning and memory in mice. Proc. Natl. Acad. Sci. U.S.A. 100, 1723-1728
Cited by
Sorted by citations
Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., Jiang, Z., Gandham, V., Friedman, B. A., Ngu, H., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.014 · Cited by 575 · see citing works
Dourlen, P., Kilinc, D., Malmanche, N., Chapuis, J., & Lambert, J.-C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02004-0 · Cited by 168 · see citing works
Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes.
Woo, E., Sansing, L. H., Arnsten, A. F. T., & Datta, D. (2021) · Chronic Stress · doi:10.1177/24705470211029254 · Cited by 159 · see citing works
Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?
Yan, Z., Kim, E., Datta, D., Lewis, D. A., & Soderling, S. H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2360-16.2016 · Cited by 120 · see citing works
Self-citationControl of dendritic spine morphological and functional plasticity by small GTPases.
Woolfrey, K. M., & Srivastava, D. P. (2016) · Neural Plasticity · doi:10.1155/2016/3025948 · Cited by 76 · see citing works
Regulation of postsynaptic signaling in structural synaptic plasticity
Fu, A. K., & Ip, N. Y. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.05.016 · Cited by 43 · see citing works
- Authors
- Spence, E. F., & Soderling, S. H.
- Affiliations
- Duke University (US)
- Corresponding author
- Soderling, Scott H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 290
- Issue
- 48
- Pages
- 28613-28622
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4661376
- OpenAlex
- W2178224525
- Cited by
- 171
- References
- 94
- Citations by year
- 2026: 3 · 2025: 17 · 2024: 15 · 2023: 10 · 2022: 18 · 2021: 24 · 2020: 18 · 2019: 15 · 2018: 18 · 2017: 19 · 2016: 12 · 2015: 2
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS059957)
- National Institute of Mental Health (MH103374, R01MH103374)
- National Institute of General Medical Sciences (T32GM007184)
- National Institute of Neurological Disorders and Stroke (R01NS059957, F31NS092402, R56NS059957, NS059957)
- 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 › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- dendritic spines, actin cytoskeleton, actin filament dynamics, spinogenesis, synaptic plasticity, neurodevelopmental disorders, mental illness, excitatory synaptic transmission
- MeSH terms
- Actins, Animals, Humans, Spinal Diseases, Spine, Synapses, Stress Fibers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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