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Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis
Open accessAbstract
Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as dendritic filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated filopodia-like protrusions. Dynamically, dendritic filopodia emerged from densities in the dendritic shaft, which by electron microscopy contained branched actin network associated with dendritic microtubules. We propose that dendritic spine morphogenesis begins from an actin patch elongating into a dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility.
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“Related surfactant-based extraction methods have provided informative access to cytoskeletal organization, including neuronal processes30–32.”
From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [30]
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“In mature neurons, they localize throughout dendritic spines,41 similar to Shank3.”
From SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism (2012) · cites this paper as [41]
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Cellular Motility Driven by Assembly and Disassembly of Actin Filaments
Pollard, T. D., & Borisy, G. G. (2003) · Cell · doi:10.1016/s0092-8674(03)00120-x · Cited by 4,334
Filopodia: molecular architecture and cellular functions
Mattila, P. K., & Lappalainen, P. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2406 · Cited by 1,699
Svitkina, T., & Borisy, G. G. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.5.1009 · Cited by 1,191
Self-citationThe ARP2/3 complex: an actin nucleator comes of age
Goley, E. D., & Welch, M. D. (2006) · Nature reviews. Molecular cell biology · doi:10.1038/nrm2026 · Cited by 1,106
The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Sheng, M., & Hoogenraad, C. C. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060805.160029 · Cited by 1,003
The lamellipodium: where motility begins
Small, J. V., Stradal, T. E. B., Vignal, E., & Rottner, K. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)02237-1 · Cited by 924
Balancing Structure and Function at Hippocampal Dendritic Spines
Bourne, J. N., & Harris, K. M. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.060407.125646 · Cited by 916
Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy.
Cingolani, L. A., & Goda, Y. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2373 · Cited by 831
The many faces of actin: matching assembly factors with cellular structures
Chhabra, E. S., & Higgs, H. N. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1110 · Cited by 779
Mechanism of filopodia initiation by reorganization of a dendritic network
Svitkina, T., Bulanova, E. A., Chaga, O. Y., Vignjevic, D. M., Kojima, S.-I., Vasiliev, J. M., & Borisy, G. G. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200210174 · Cited by 769
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Items 401–413 of 413
CIL:40663, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40663
Self-citationCIL:41104, Chlorocebus aethiops. In Cell Image Library
Planchon, T. A., Gao, L., Milkie, D. E., Davidson, M. W., Galbraith, J. A., & Galbraith, C. G. (2012) · UC San Diego · doi:10.7295/w9cil41104
CIL:40664, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40664
Self-citationCIL:40810, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40810
Self-citationCIL:40666, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40666
Self-citationCIL:40667, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40667
Self-citationCIL:40952, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40952
Self-citationCIL:40662, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40662
Self-citationCIL:40660, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40660
Self-citationCIL:40659, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40659
Self-citationCIL:40665, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40665
Self-citationCIL:40804, Rattus, hippocampal neuron. In Cell Image Library
Korobova, F., & Svitkina, T. (2012) · UC San Diego · doi:10.7295/w9cil40804
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Metadata
- Authors
- Korobova, F., & Svitkina, T.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Svitkina, Tatyana
- Venue
- Molecular Biology of the Cell
- Published
- 2010-01
- Volume
- 21
- Issue
- 1
- Pages
- 165-176
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2801710
- OpenAlex
- W2031516445
- Cited by
- 399
- References
- 51
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 19 · 2023: 22 · 2022: 21 · 2021: 25 · 2020: 28 · 2019: 23 · 2018: 30 · 2017: 24 · 2016: 30 · 2015: 27 · 2014: 36 · 2013: 34 · 2012: 27
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM070898, GM 70898)
- National Center for Research Resources (RR-22482, S10RR022482)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- dendritic spine morphogenesis, hippocampal neurons, Arp2/3 complex, capping protein, myosin II, dendritic filopodia, presynaptic terminals, actin filament nucleation, microtubules, excitatory synapses
- MeSH terms
- Actins, Cytoskeletal Proteins, Cytoskeleton, Fluorescent Antibody Technique, Hippocampus, Models, Biological, Pseudopodia, Synapses, Biomarkers, Cell Shape, Dendritic Spines
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