Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways
Open accessAbstract
Dendritic arborization and spine formation are critical for the functioning of neurons. Although many proteins have been identified recently as regulators of dendritic morphogenesis, the intracellular signaling pathways that control these processes are not well understood. Here we report that the Ras-phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway plays pivotal roles in the regulation of many aspects of dendrite formation. Whereas the PI3K-Akt-mTOR pathway alone controlled soma and dendrite size, a coordinated activation together with the Ras-mitogen-activated protein kinase signaling pathway was required for increasing dendritic complexity. Chronic inhibition of PI3K or mTOR reduced soma and dendrite size and dendritic complexity, as well as density of dendritic filopodia and spines, whereas a short-term inhibition promoted the formation of mushroom-shaped spines on cells expressing constitutively active mutants of Ras, PI3K, or Akt, or treated with the upstream activator BDNF. Together, our data underscore the central role of a spatiotemporally regulated key cell survival and growth pathway on trophic regulation of the coordinated development of dendrite size and shape.
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PI3K/AKT, RAS/ERK, WNT and β-catenin pathways control soma size, dendritic arborization, axon generation, spine development and synapse function.
“These pathways control soma size, dendritic arborization, axon generation, spine development and synapse function [184–188].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [184]
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- Authors
- Kumar, V., Zhang, M.-X., Swank, M. W., Kunz, J., & Wu, G.-Y.
- Affiliations
- Baylor College of Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-12-07
- Volume
- 25
- Issue
- 49
- Pages
- 11288-11299
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725910
- OpenAlex
- W2130139152
- Cited by
- 588
- References
- 6
- Citations by year
- 2026: 7 · 2025: 27 · 2024: 21 · 2023: 28 · 2022: 31 · 2021: 22 · 2020: 36 · 2019: 30 · 2018: 33 · 2017: 36 · 2016: 41 · 2015: 28 · 2014: 30 · 2013: 47 · 2012: 48
- FWCI
- 5.54
- 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
- U.S. Army (W81XWH-04-1-0260, W81XWH)
- U.S. Public Health Service (DA17919)
- National Institute on Drug Abuse (R21DA017919, DA17919)
- National Institute of General Medical Sciences (R01GM068098, GM 068098)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- dendrite morphogenesis, dendritic spine formation, RAS/MAPK pathway, dendritic complexity, dendritic filopodia, brain-derived neurotrophic factor, dendrite size, neuronal development, cell survival signaling
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Cells, Cultured, Dendrites, Enzyme Activation, Enzyme Inhibitors, Morphogenesis, Protein Kinases, Signal Transduction, ras Proteins, Phosphatidylinositol 3-Kinases, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Signaling System, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases, In Vitro Techniques
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