Activity-Dependent Redistribution and Essential Role of Cortactin in Dendritic Spine Morphogenesis
Open accessAbstract
The number and shape of dendritic spines are influenced by activity and regulated by molecules that organize the actin cytoskeleton of spines. Cortactin is an F-actin binding protein and activator of the Arp2/3 actin nucleation machinery that also interacts with the postsynaptic density (PSD) protein Shank. Cortactin is concentrated in dendritic spines of cultured hippocampal neurons, and the N-terminal half of the protein containing the Arp2/3 and F-actin binding domains is necessary and sufficient for spine targeting. Knockdown of cortactin protein by short-interfering RNA (siRNA) results in depletion of dendritic spines in hippocampal neurons, whereas overexpression of cortactin causes elongation of spines. In response to synaptic stimulation and NMDA receptor activation, cortactin redistributes rapidly from spines to dendritic shaft, correlating with remodeling of the actin cytoskeleton, implicating cortactin in the activity-dependent regulation of spine morphogenesis.
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Spines contain unusually high levels of actin.
“Indeed, spines contain unusually high levels of actin (307–309)”
From Synaptic memory and CaMKII (2023) · cites this paper as [309]
Shank proteins can bind to several actin-regulatory molecules, such as cortactin, Sharpin, alpha-fodrin, Abp1, beta-Pix and SPAR.
“In addition, Shank proteins can bind to several actin-regulatory molecules, such as cortactin,13, 14 Sharpin,15 α-fodrin,16 Abp1,17 β-Pix18 and SPAR.19”
From SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism (2012) · cites this paper as [13]
Shank3 binds to cortactin and loss of cortactin causes a decrease in spine density.
“As Shank3 binds to cortactin and the loss of cortactin causes a decrease in spine density,12, 13, 21 we examined the effect of each mutation on cortactin content in dendritic spines.”
From SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism (2012) · cites this paper as [13]
Depletion of the Arp2/3 complex components (cortactin, Abi2, WAVE-1, N-WASP, Abp1) alters spine morphology and number.
“Indeed, depletion of the Arp2/3 complex, including cortactin, Abi2, WAVE–1, N–WASP and Abp1, alters the morphology and number of spines.13, 42, 43, 44, 45”
From SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism (2012) · cites this paper as [13]
Cortactin mediates neurite outgrowth.
“cortactin mediates neurite outgrowth,13”
From SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism (2012) · cites this paper as [13]
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- Authors
- Hering, H., & Sheng, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Sheng, Morgan
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-12-17
- Volume
- 23
- Issue
- 37
- Pages
- 11759-11769
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6740953
- OpenAlex
- W1580592479
- Cited by
- 269
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 16 · 2014: 19 · 2013: 16 · 2012: 24
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Directorate for Biological Sciences
- National Institute of Child Health and Human Development
- 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
- cortactin, dendritic spine morphogenesis, actin cytoskeleton, Arp2/3 complex, F-actin binding, shank, postsynaptic density, hippocampal neurons, NMDA receptor, synaptic activity, actin cytoskeleton remodeling
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Hippocampus, Microfilament Proteins, Neurons, Receptors, N-Methyl-D-Aspartate, Protein Structure, Tertiary, Glutamic Acid, Protein Transport, RNA Interference, Cortactin, Rats
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