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Different Roles for RhoA During Neurite Initiation, Elongation, and Regeneration in PC12 Cells
Author(s) -
Sebök Ágnes,
Nusser Nóra,
Debreceni Balázs,
Guo Zhong,
Santos Marinilce F.,
Szeberenyi József,
Tigyi Gábor
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730949.x
Subject(s) - neurite , rhoa , microbiology and biotechnology , nerve growth factor , biology , regeneration (biology) , morphogenesis , signal transduction , extracellular , receptor , in vitro , biochemistry , gene
: 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.