Control of Dendritic Arborization by the Phosphoinositide-3′-Kinase–Akt–Mammalian Target of Rapamycin Pathway

By J. Jaworski, S. Spangler, Daniel P. Seeburg, C. Hoogenraad, M. Sheng. Journal of Neuroscience, 2005

595 citations recorded by the source corpus.

The molecular mechanisms that determine the size and complexity of the neuronal dendritic tree are unclear. Here, we show that the phosphoinositide-3′ kinase (PI3K)–Akt–mammalian target of rapamycin (mTOR) signaling pathway promotes the growth and branching of dendrites in cultured hippocampal neurons. Constitutively active mutants of Ras, PI3K, and Akt, or RNA interference (RNAi) knockdown of lipid phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome Ten), induced growth and elaboration of dendrites that was blocked by mTOR inhibitor rapamycin and/or by overexpression of eIF-4E binding protein 1 (4E-BP1), which inhibits translation of 5′ capped mRNAs. The effect of PI3K on dendrites was lost in more mature neurons (>14 d in vitro). Dendritic complexity was reduced by inhibition of PI3K and by RNAi knockdown of mTOR or p70 ribosomal S6 kinase (p70S6K, an effector of mTOR). A rapamycin-resistant mutant of mTOR “rescued” the morphogenetic effects of PI3K in the presence of rapamycin. By regulating global and/or local protein translation, and as a convergence point for multiple signaling pathways, mTOR could play a central role in the control of dendrite growth and branching during development and in response to activity.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bd99d448a6a4f4772ac09d800f56b88dbcaecc07

How researchers see this paper

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In Cancer Research

1. G. Lietzau
2. Janusz Morys
3. E. Czuba
4. Monika Waskow
5. A. Steliga
6. P. Kowiański

In Molecular Biology

1. Suzanne J. Baker
2. G. Lietzau
3. Janusz Morys
4. E. Czuba
5. Monika Waskow
6. A. Steliga
7. P. Kowiański
8. T. Franke

Citations in the corpus

• BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity (2017, background): “The PI3K/Akt/mTOR cascade, through regulation of protein synthesis and cytoskeleton development, enhances dendritic growth and branching (Jaworski et al. 2005; Kumar et al. 2005).”
• Psychedelics Promote Structural and Functional Neural Plasticity (2018, background): “Jones et al. (2009) demonstrated that DOI was capable of transiently increasing the size of dendritic spines on cortical neurons, but no change in spine density was observed.”
• DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212 (2009, unknown): “…regulate diverse processes of neuronal development, including morphogenesis, dendritic development, synapse formation, and synaptic plasticity (Atwal et al., 2000; Jaworski et al., 2005; Jiang et al., 2005; Kuruvilla et al., 2000; Markus et al., 2002; Sanna et al., 2002; Yoshimura et al., 2006).”
• Pten regulates neuronal arborization and social interaction in mice. (2006, background): “In primary neuron cultures, the PI3K pathway regulates cell survival, neurite growth, and dendritic arborization (Crowder and Freeman, 1998; Jaworski et al., 2005; Klesse and Parada, 1998; Markus et al., 2002).”