Neurite outgrowth from PC12 cells by basic fibroblast growth factor (bFGF) is mediated by RhoA inactivation through p190RhoGAP and ARAP3
| Autor: | Jae-Bong Park, Jeffrey Settleman, Nozomu Mori, Hiroshi Morii, Jae-Yong Lee, Jaebong Kim, Chan-Young Jeon, Hee-Jun Kim, Sung Chan Kim |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
RHOA
Neurite Physiology Clinical Biochemistry Basic fibroblast growth factor Hippocampus PC12 Cells chemistry.chemical_compound Lysophosphatidic acid Neurites Animals Cells Cultured Adaptor Proteins Signal Transducing Neurons biology Chemistry GTPase-Activating Proteins Signal transducing adaptor protein Cell Biology Molecular biology Rats Cell biology Repressor Proteins Cell culture biology.protein Exoenzyme Fibroblast Growth Factor 2 rhoA GTP-Binding Protein Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Cellular Physiology. 224:786-794 |
| ISSN: | 0021-9541 |
| DOI: | 10.1002/jcp.22184 |
| Popis: | The rat pheochromocytoma cell line PC12 has been widely used as a model to study neuronal differentiation. PC12 cells give rise to neurites in response to basic fibroblast growth factor (bFGF). However, it is unclear whether bFGF promotes neurite outgrowth by inducing RhoA inactivation, and a mechanism for RhoA inactivation in PC12 cells in response to bFGF has not been reported. Lysophosphatidic acid (LPA) treatment and the expression of constitutively active (CA)-RhoA (RhoA V14) impaired neurite formation in response to bFGF, while Tat-C3 exoenzyme and the expression of dominant negative (DN)-RhoA (RhoA N19) stimulated neurite outgrowth. GTP-bound RhoA levels were reduced in response to bFGF, which suggests that the inactivation of RhoA is essential to neurite outgrowth in response to bFGF. To investigate the mechanism of RhoA inactivation, this study examined the roles of p190RhoGAP and Rap-dependent RhoGAP (ARAP3). DN-p190RhoGAP prevented neurite outgrowth, while WT-p190RhoGAP and Src synergistically stimulated neurite outgrowth; these findings suggest that bFGF promotes the inactivation of RhoA and subsequent neurite outgrowth through p190RhoGAP and Src. Furthermore, DN-Rap1 and DN-ARAP3 reduced neurite formation in PC12 cells. These results suggest that RhoA is likely to be inactivated by p190RhoGAP and ARAP3 during neurite outgrowth in response to bFGF. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text