Dock4 regulates dendritic development in hippocampal neurons.
Abstract
Dendrite development is required for establishing proper neuronal connectivity. Rho-family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up-regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C-terminal Crk-binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons.
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Dock4 is important for neuronal development and social behaviors.
“Dock4 is important for neuronal development and social behaviors.”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Ueda et al., 2008
Dock4 is important for neurite outgrowth and synapse morphogenesis during neuronal development.
“Previous evidence has revealed that Dock4 is important for neurite outgrowth and synapse morphogenesis during neuronal development (Ueda et al., 2008, 2013; Xiao et al., 2013).”
From Two Autism/Dyslexia Linked Variations of DOCK4 Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development (2020) · cites this paper as Ueda et al., 2008
Dock4 plays critical roles in axon guidance, dendritic development, and dendritic spine formation, but these results were obtained from in vitro preparations.
“Dock4 has been found to plays critical roles in axon guidance, dendritic development, and dendritic spine formation, but these results were obtained from in vitro preparations 27, 29–31.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [29]
Cites
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Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
Brugnera, E., Haney, L., Grimsley, C., Lu, M., Walk, S. F., Tosello-Trampont, A.-C., Macara, I. G., Madhani, H., Fink, G. R., & Ravichandran, K. S. (2002) · Nature Cell Biology · doi:10.1038/ncb824 · Cited by 576 · see citing works
Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development
Rosso, S. B., Sussman, D., Wynshaw-Boris, A., & Salinas, P. C. (2005) · Nature Neuroscience · doi:10.1038/nn1374 · Cited by 485 · cited 4× · see citing works
“, 2002), whereas enhanced Rac activity promotes dendritic growth and branching (Li et al., 2000; Wong et al., 2000; Rosso et al., 2005).”
BackgroundMethodInfluentialZizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller, N., Irani-Tehrani, M., Kiosses, W. B., Del Pozo, M. A., & Schwartz, M. A. (2002) · Nature Cell Biology · doi:10.1038/ncb835 · Cited by 171 · see citing works
A novel mechanism for the regulation of amyloid precursor protein metabolism
Chen, Q., Kimura, H., & Schubert, D. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110151 · Cited by 63 · see citing works
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Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops
Mullins, C., Fishell, G., & Tsien, R. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.017 · Cited by 167 · see citing works
A review of the evidence for the canonical Wnt pathway in autism spectrum disorders
Kalkman, H. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-10 · Cited by 142 · see citing works
Guo, D., Peng, Y., Wang, L., Sun, X., Wang, X., Liang, C., Yang, X., Li, S., Xu, J., Ye, W.-C., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-019-0472-7 · Cited by 102 · see citing works
Xiao, Y., Peng, Y., Wan, J., Tang, G., Chen, Y., Tang, J., Ye, W.-C., Ip, N. Y., & Shi, L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.458612 · Cited by 71 · see citing works
Mukherjee, K., Edgett, B. A., Burrows, H. W., Castro, C., Griffin, J. L., Schwertani, A. G., Gurd, B. J., & Funk, C. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092031 · Cited by 65 · see citing works
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“Moreover, Dock4 is suggested to play important roles in neuronal development such as axon guidance, dendrite development and dendritic spine morphogenesis (Ueda et al., 2008, 2013; Xiao et al., 2013; Makihara et al., 2018).”
BackgroundThompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
“Knockdown of DOCK4 with shRNA eliminates dendritic growth and branching in hippocampal neurons (83).”
Background
- Authors
- Ueda, S., Fujimoto, S., Hiramoto, K., Negishi, M., & Katoh, H.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Katoh, Hironori
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2008-07-09
- Volume
- 86
- Issue
- 14
- Pages
- 3052-3061
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2068850673
- Cited by
- 61
- References
- 5
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 8 · 2020: 1 · 2019: 4 · 2018: 2 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- DOCK4, dendritic development, dendritic branching, hippocampal neurons, CrkII, dendrite morphogenesis, neuronal development, Rho GTPases
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Dendrites, Fluorescent Antibody Technique, Hippocampus, Neurons, Blotting, Western, Rats, Wistar, In Situ Hybridization, GTPase-Activating Proteins, Immunoprecipitation, Proto-Oncogene Proteins c-crk, Rats
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