Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons

In Jung Kim, Karen M. Drahushuk, Woo Yang Kim, Eugene A. Gonsiorek, Pamela J Lein, Douglas A. Andres, Dennis Higgins

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

NGF activates several signaling cascades in sympathetic neurons. We examined how activation of one of these cascades, the ERK/MAP (extracellular signal-regulated kinase/mitogen-activated protein) kinase pathway, affects dendritic growth in these cells. Dendritic growth was induced by exposure to NGF and BMP-7 (bone morphogenetic protein-7). Exposure to NGF increased phosphorylation of ERK1/2. Unexpectedly, two MEK (MAP kinase kinase) inhibitors (PD 98059 and U 0126) enhanced dendritic growth, and a ligand, basic FGF, that activates the ERK pathway inhibited the growth of these processes. The enhancement of dendritic growth by PD 98059 was associated with an increase in the number of axo-dendritic synapses, and it appeared to represent a specific morphogenic effect because neither axonal growth nor cell survival was affected. In addition, increased dendritic growth was not observed after exposure to inhibitors of other signaling pathways, including the phosphatidylinositol-3-kinase inhibitor LY 294002. Dendritic growth was also increased in cells transfected with dominant-negative mutants of MEK1 and ERK2 but not with dominant-negative mutants of MEK5 and ERK5, suggesting that ERK1/2 is the primary mediator of this effect. Exposure to BMP-7 induces nuclear translocation of SmadI (Sma- and Mad-related protein 1), and PD 98059 treatment potentiated nuclear accumulation of Smad-1 induced by BMP-7 in sympathetic neurons, suggesting a direct enhancement of BMP signaling in cells treated with an MEK inhibitor. These observations indicate that one of the signaling cascades activated by NGF can act in an antagonistic manner in sympathetic neurons and reduce the dendritic growth induced by other NGF-sensitive pathways.

Original languageEnglish (US)
Pages (from-to)3304-3312
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number13
DOIs
StatePublished - Mar 31 2004
Externally publishedYes

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Extracellular Signal-Regulated MAP Kinases
Neurons
Nerve Growth Factor
Growth
Bone Morphogenetic Protein 7
Mitogen-Activated Protein Kinase Kinases
Smad Proteins
Phosphatidylinositol 3-Kinase
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
MAP Kinase Signaling System
Mitogen-Activated Protein Kinases
Synapses
Cell Survival
Phosphorylation
Ligands

Keywords

  • BMP
  • Dendrite
  • ERK
  • MAP kinase
  • MEK
  • NGF

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, I. J., Drahushuk, K. M., Kim, W. Y., Gonsiorek, E. A., Lein, P. J., Andres, D. A., & Higgins, D. (2004). Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons. Journal of Neuroscience, 24(13), 3304-3312. https://doi.org/10.1523/JNEUROSCI.3286-03.2004

Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons. / Kim, In Jung; Drahushuk, Karen M.; Kim, Woo Yang; Gonsiorek, Eugene A.; Lein, Pamela J; Andres, Douglas A.; Higgins, Dennis.

In: Journal of Neuroscience, Vol. 24, No. 13, 31.03.2004, p. 3304-3312.

Research output: Contribution to journalArticle

Kim, IJ, Drahushuk, KM, Kim, WY, Gonsiorek, EA, Lein, PJ, Andres, DA & Higgins, D 2004, 'Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons', Journal of Neuroscience, vol. 24, no. 13, pp. 3304-3312. https://doi.org/10.1523/JNEUROSCI.3286-03.2004
Kim, In Jung ; Drahushuk, Karen M. ; Kim, Woo Yang ; Gonsiorek, Eugene A. ; Lein, Pamela J ; Andres, Douglas A. ; Higgins, Dennis. / Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 13. pp. 3304-3312.
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