A WAVE-1 and WRP Signaling Complex Regulates Spine Density, Synaptic Plasticity, and Memory
Open accessAbstract
The scaffolding protein WAVE-1 (Wiskott-Aldrich syndrome protein family member 1) directs signals from the GTPase Rac through the Arp2/3 complex to facilitate neuronal actin remodeling. The WAVE-associated GTPase activating protein called WRP is implicated in human mental retardation, and WAVE-1 knock-out mice have altered behavior. Neuronal time-lapse imaging, behavioral analyses, and electrophysiological recordings from genetically modified mice were used to show that WAVE-1 signaling complexes control aspects of neuronal morphogenesis and synaptic plasticity. Gene targeting experiments in mice demonstrate that WRP anchoring to WAVE-1 is a homeostatic mechanism that contributes to neuronal development and the fidelity of synaptic connectivity. This implies that signaling through WAVE-1 complexes is essential for neural plasticity and cognitive behavior.
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Genetic ablation of WRC components affects spine morphology and excitability.
“Rearrangements of the actin cytoskeleton strongly influence the formation, retraction, motility, stability, and shape of the dendritic spines (Tada and Sheng, 2006), and genetic ablation of WRC components affects spine morphology and excitability (Grove et al., 2004, Kim et al., 2006, Soderling et al., 2007, Wiens et al., 2005).”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Soderling et al., 2007
The Discussion (page unavailable) reports reduced spine density in WAVE-1 knock-out mice. The section “Loss of WAVE-1 alters synaptic plasticity” (page unavailable) reports altered synaptic transmission and plasticity, including reduced maximal fEPSPs, but does not establish a change in neuronal excitability specifically. The paper therefore supports the spine finding and a related functional change, not the full claim as phrased. (LLM, conf=0.82)
Experimental — accuracy not yet measuredWAVE1 deletion decreases the density and alters the morphology of dendritic spines.
“WAVE1 deletion decreases the density and alters the morphology of dendritic spines22,61.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [61]
In “WAVE-1 plays a role in the development of dendritic spines,” WAVE-1-null mice have reduced spine density in the hippocampus and cortex. The spine-shape change reported in “Characterization of mWAVE-1 mice” was observed in neurons transfected with a dominant-interfering WAVE-1 mutant, not in the deletion mice; the source therefore does not establish that deletion alters spine morphology. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSeveral genes involved in synaptic plasticity, synaptic transmission, and long-term potentiation (Gria1, Grin2b, Wasf1) showed low expression in WT, ApoeCh, and PS19, but were upregulated in PS19;ApoeCh.
“There were also several genes (i.e., Gria1, Grin2b, Wasf1), involved in synaptic plasticity, synaptic transmission, and long-term potentiation that showed low expression in WT, ApoeCh, and PS19, but which were upregulated in PS19;ApoeCh (Fig. 8c) [70–73].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [73]
The observed spine dysmorphogenesis is in line with defects in WRC components, loss of FMRP, overexpression of ARC, or Rac1 blockade during early development.
“the observed spine dysmorphogenesis is in line with defects in the WRC components (Grove et al., 2004, Kim et al., 2006, Soderling et al., 2007), loss of FMRP (Comery et al., 1997, Cruz-Martín et al., 2010, Galvez and Greenough, 2005, Irwin et al., 2002), overexpression of ARC (Peebles et al., 2010), or Rac1 blockade during early development (Tashiro and Yuste, 2004).”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Soderling et al., 2007
WAVE1 also regulates growth cone dynamics and neurite outgrowth in cultured neurons.
“WAVE1 also regulates growth cone dynamics and neurite outgrowth in cultured neurons61 (Fig. 4a).”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [61]
The WAVE1 complex is localized to dendritic spines and plays an important role in the regulation of dendritic spine morphology.
“The WAVE1 complex is localized to dendritic spines and plays an important role in the regulation of dendritic spine morphology.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [61]
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Cites
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Research works printed but not linked: 2
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Actin Out: Regulation of the Synaptic Cytoskeleton
Spence, E. F., & Soderling, S. H. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.655118 · Cited by 171 · see citing works
Self-citationPlasticity of dendritic spines: subcompartmentalization of signaling
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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-citationCYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome
Abekhoukh, S., & Bardoni, B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00081 · Cited by 110 · see citing works
Control 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
Dendritic spine actin cytoskeleton in autism spectrum disorder
Joensuu, M., Lanoue, V., & Hotulainen, P. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.023 · Cited by 65 · see citing works
Khanal, P., & Hotulainen, P. (2021) · Cells · doi:10.3390/cells10092392 · Cited by 60 · see citing works
Tran, K. M., Kwang, N. E., Butler, C. A., Gomez-Arboledas, A., Kawauchi, S., Mar, C., Chao, D., Barahona, R. A., Da Cunha, C., Tsourmas, K. I., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00793-x · Cited by 28 · see citing works
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Soderling, S. H., Guire, E. S., Kaech, S., White, J., Zhang, F., Schutz, K., Langeberg, L. K., Banker, G., Raber, J., & Scott, J. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Oregon Health & Science University (US)
- Oregon National Primate Research Center (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-01-10
- Volume
- 27
- Issue
- 2
- Pages
- 355-365
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3740594
- OpenAlex
- W1973155317
- Cited by
- 217
- References
- 1
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 12 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 12 · 2015: 8 · 2014: 23 · 2013: 24 · 2012: 12
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG-NS-0201, DK44239)
- National Institute on Aging (R01AG020904, AG20904)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK044239, DK44239)
- National Institute of Neurological Disorders and Stroke (R01NS027037, NS 17112, R01NS017112, NS 27037)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Arp2/3 complex, Rac GTPase, actin cytoskeleton remodeling, dendritic spine density, synaptic plasticity, memory, neuronal morphogenesis, synaptic connectivity, cognitive behavior
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Homeostasis, Humans, Memory, Mice, Inbred C57BL, Molecular Sequence Data, Synaptic Transmission, Neuronal Plasticity, Signal Transduction, Rats, Sprague-Dawley, Mice, Knockout, GTPase-Activating Proteins, Dendritic Spines, Wiskott-Aldrich Syndrome Protein Family, Mice, Rats
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