Cited by 413Neuroscience and Neuropharmacology ResearchCellular Mechanics and InteractionsGenetics and Neurodevelopmental Disorders

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Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis

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Korobova, Farida, Svitkina, Tatyana·2010·Molecular Biology of the Cell

DOI 10.1091/mbc.e09-07-0596PMC PMC2801710

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Abstract

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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Authors: Korobova, F., & Svitkina, T.
Affiliations: University of Pennsylvania (US)
Corresponding author: Svitkina, Tatyana
ORCID: Korobova, Farida
Svitkina, Tatyana
Venue: Molecular Biology of the Cell
Publisher: American Society for Cell Biology (ASCB)
Published: 2010-01
Volume: 21
Issue: 1
Pages: 165-176
ISSN: 1059-1524 (ISSN-L)
1939-4586
DOI: 10.1091/mbc.e09-07-0596
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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Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis

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