Different roles for RhoA during neurite initiation, elongation, and regeneration in PC12 cells

Ágnes Sebök, Nóra Nusser, Balázs Debreceni, Zhong Guo, Marinilce F. Santos, József Szeberenyi, Gabor Tigyi

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The goal of the present study was to characterize the effects of RhoA at different stages of nerve growth factor (NGF)-induced neuronal differentiation in the PC12 model. This comparative analysis was prompted by previous studies that reported apparently opposite effects for Rho in different models of neuronal differentiation and regeneration. PC12 cells were transfected with activated V14RhoA or dominant negative N19RhoA under the control of either a constitutive or a steroid-regulated promoter. Upon exposure to NGF, V14RhoA cells continued to proliferate and did not extend neurites; however, they remained responsive to NGF, as indicated by the activation of extracellular signal-regulated kinases. This inability to differentiate was reversed by C3 toxin and activation of cyclic AMP signaling, which inactivate RhoA. N19RhoA expression led to an increase in neurite initiation and branching. In contrast, when the RhoA mutants were expressed after NGF priming, only the rate of neurite extension was altered; V14RhoA clones had neurites approximately twice as long, whereas neurites of N19RhoA cells were ~50% shorter than those of appropriate controls. The effects of Rho in neurite regeneration mimicked those observed during the initial stages of morphogenesis; activation inhibited, whereas inactivation promoted, neurite outgrowth. Our results indicate that RhoA function changes at different stages of NGF-induced neuronal differentiation and neurite regeneration.

Original languageEnglish (US)
Pages (from-to)949-960
Number of pages12
JournalJournal of Neurochemistry
Volume73
Issue number3
DOIs
StatePublished - Aug 30 1999

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PC12 Cells
Nerve Growth Factor
Neurites
rhoA GTP-Binding Protein
Regeneration
Elongation
Chemical activation
Extracellular Signal-Regulated MAP Kinases
Cyclic AMP
Steroids
Morphogenesis
Clone Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Different roles for RhoA during neurite initiation, elongation, and regeneration in PC12 cells. / Sebök, Ágnes; Nusser, Nóra; Debreceni, Balázs; Guo, Zhong; Santos, Marinilce F.; Szeberenyi, József; Tigyi, Gabor.

In: Journal of Neurochemistry, Vol. 73, No. 3, 30.08.1999, p. 949-960.

Research output: Contribution to journalArticle

Sebök, Ágnes ; Nusser, Nóra ; Debreceni, Balázs ; Guo, Zhong ; Santos, Marinilce F. ; Szeberenyi, József ; Tigyi, Gabor. / Different roles for RhoA during neurite initiation, elongation, and regeneration in PC12 cells. In: Journal of Neurochemistry. 1999 ; Vol. 73, No. 3. pp. 949-960.
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