ARF6 and EFA6A Regulate the Development and Maintenance of Dendritic Spines
Open accessAbstract
The cellular and molecular mechanisms underlying the development and maintenance of dendritic spines are not fully understood. ADP-ribosylation factor 6 (ARF6) is a small GTPase known to regulate actin remodeling and membrane traffic. Here, we report involvement of ARF6 and exchange factor for ARF6 (EFA6A) in the regulation of spine development and maintenance. An active form of ARF6 promotes the formation of dendritic spines at the expense of filopodia. EFA6A promotes spine formation in an ARF6 activation-dependent manner. Knockdown of ARF6 and EFA6A by small interfering RNA decreases spine formation. Live imaging indicates that ARF6 knockdown decreases the conversion of filopodia to spines and the stability of early spines. The spine-promoting effect of ARF6 is partially blocked by Rac1. ARF6 and EFA6A protect mature spines from inactivity-induced destabilization. These results suggest that ARF6 and EFA6A may regulate the conversion of filopodia to spines and the stability of both early and mature spines.
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Members of the ARF family of small GTPases and their regulators are important regulators of spine density and morphology.
“Members of the ADP-ribosylation factor (ARF) family of small GTPases and their regulators have gained increasing attention as important regulators of spine density and morphology [27], [28], [29].”
From Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development (2012) · cites this paper as [27]
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Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H. (2001) · Nature Neuroscience · doi:10.1038/nn736 · Cited by 1,563 · cited 1× · see citing works
“Rac1-dependent regulation of actin rearrangement and spine dimensions has been closely associated with the modulation of synaptic strength and plasticity (Matsuzaki et al., 2001; Yuste and Bonhoeffer , 2001; Hayashi and Majewska, 2005; Matus, 2005; Segal, 2005).”
Dendritic spines and long-term plasticity
Segal, M. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1649 · Cited by 489 · see citing works
Penzes, P., Beeser, A., Chernoff, J., Schiller, M. R., Eipper, B. A., Mains, R. E., & Huganir, R. L. (2003) · Neuron · doi:10.1016/s0896-6273(02)01168-6 · Cited by 466 · see citing works
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Warnet, X. L., Bakke Krog, H., Sevillano‐Quispe, O. G., Poulsen, H., & Kjaergaard, M. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14842 · Cited by 50 · see citing works
Arf4 Determines Dentate Gyrus-Mediated Pattern Separation by Regulating Dendritic Spine Development
Jain, S., Yoon, S. Y., Zhu, L., Brodbeck, J., Dai, J., Walker, D., & Huang, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046340 · Cited by 43 · see citing works
Waller, J. A., Chen, F., & Sánchez, C. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.12.012 · Cited by 25 · see citing works
- Authors
- Choi, S., Ko, J., Lee, J.-R., Lee, H. W., Kim, K., Chung, H. S., Kim, H., & Kim, E.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Korea University (KR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-05-03
- Volume
- 26
- Issue
- 18
- Pages
- 4811-4819
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674147
- OpenAlex
- W1974330164
- Cited by
- 101
- References
- 3
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 13 · 2019: 4 · 2018: 2 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 9
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KAIST Institutional Repository (KAIST) (submittedVersion)
- Funders
- National Institutes of Health (-0001)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- ARF6, dendritic spines, spine development, spinal stability, filopodia, small GTPases, actin cytoskeleton remodeling, Rac1, synaptic plasticity
- MeSH terms
- Disks Large Homolog 4 Protein, ADP-Ribosylation Factor 6, Anesthetics, Local, Animals, Animals, Newborn, Brain, Cells, Cultured, Diagnostic Imaging, Drug Interactions, Embryo, Mammalian, Enzyme Activation, Hippocampus, Immunohistochemistry, Membrane Proteins, Neurons, Pseudopodia, Tetrodotoxin, Time Factors, Transfection, Blotting, Northern, Mutagenesis, Gene Expression Regulation, Developmental, Guanine Nucleotide Exchange Factors, ADP-Ribosylation Factors, RNA, Small Interfering, Intracellular Signaling Peptides and Proteins, Dendritic Spines, Green Fluorescent Proteins, Rats
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