Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways

Vikas Kumar, Ming Xiang Zhang, Michael W. Swank, Jeannette Kunz, Gang Yi Wu

Research output: Contribution to journalArticle

363 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11288-11299
Number of pages12
JournalJournal of Neuroscience
Volume25
Issue number49
DOIs
Publication statusPublished - Dec 7 2005
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Sirolimus
Dendrites
Morphogenesis
Dendritic Spines
Carisoprodol
Pseudopodia
Neuronal Plasticity
Agaricales
Brain-Derived Neurotrophic Factor
Mitogen-Activated Protein Kinases
Cell Survival
Spine
Neurons
Growth
Proteins

Keywords

  • BDNF
  • Confocal microscopy
  • Dendrite development
  • Hippocampal cultures
  • Ras signaling
  • Size control

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways. / Kumar, Vikas; Zhang, Ming Xiang; Swank, Michael W.; Kunz, Jeannette; Wu, Gang Yi.

In: Journal of Neuroscience, Vol. 25, No. 49, 07.12.2005, p. 11288-11299.

Research output: Contribution to journalArticle

Kumar, Vikas ; Zhang, Ming Xiang ; Swank, Michael W. ; Kunz, Jeannette ; Wu, Gang Yi. / Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 49. pp. 11288-11299.
@article{23d9ad3ea15d433497639574fbbb5c77,
title = "Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways",
abstract = "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.",
keywords = "BDNF, Confocal microscopy, Dendrite development, Hippocampal cultures, Ras signaling, Size control",
author = "Vikas Kumar and Zhang, {Ming Xiang} and Swank, {Michael W.} and Jeannette Kunz and Wu, {Gang Yi}",
year = "2005",
month = "12",
day = "7",
doi = "10.1523/JNEUROSCI.2284-05.2005",
language = "English",
volume = "25",
pages = "11288--11299",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "49",

}

TY - JOUR

T1 - Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways

AU - Kumar, Vikas

AU - Zhang, Ming Xiang

AU - Swank, Michael W.

AU - Kunz, Jeannette

AU - Wu, Gang Yi

PY - 2005/12/7

Y1 - 2005/12/7

N2 - 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.

AB - 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.

KW - BDNF

KW - Confocal microscopy

KW - Dendrite development

KW - Hippocampal cultures

KW - Ras signaling

KW - Size control

UR - http://www.scopus.com/inward/record.url?scp=30544442753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30544442753&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.2284-05.2005

DO - 10.1523/JNEUROSCI.2284-05.2005

M3 - Article

VL - 25

SP - 11288

EP - 11299

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 49

ER -