Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways

By Vikas Kumar, Mingxu Zhang, M. Swank, J. Kunz, Gang-yi Wu. Journal of Neuroscience, 2005

606 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/284980f68737430ce9b85eec734c446a7174fbec

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. C. Björkholm
2. G. Lietzau
3. Janusz Morys
4. E. Czuba
5. L. Monteggia
6. Monika Waskow
7. A. Steliga
8. P. Kowiański

In Molecular Biology

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

Citations in the corpus

• Psychedelics Promote Structural and Functional Neural Plasticity (2018, background): “, 2004), which plays a key role in structural plasticity (Jaworski et al., 2005; Kumar et al., 2005), the production of proteins necessary for synaptogenesis (Hoeffer and Klann, 2010), and the effects of ketamine (Dwyer and Duman, 2013; Li et al.”
• BDNF — a key transducer of antidepressant effects (2015, background): “Activity-dependent BDNF transcription can also be regulated by epigenetic changes of the chromatin structure, adding yet another level of regulation (Kumar et al., 2005; Zhou et al., 2006).”
• 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).”