Rac1 and Rac3 have opposing functions in cell adhesion and differentiation of neuronal cells
| Autor: | John G. Collard, Saskia van Es, Babet van der Vaart, Saskia I.J. Ellenbroek, Amra Hajdo-Milasinovic |
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| Rok vydání: | 2007 |
| Předmět: |
rac1 GTP-Binding Protein
Cell type RHOA Role of cell adhesions in neural development Cell Down-Regulation Fluorescent Antibody Technique RAC1 Biology Culture Media Serum-Free Cell Line Tumor medicine Cell Adhesion Humans Small GTPase RNA Messenger RNA Small Interfering Cell adhesion Neurons Cell Differentiation Cell Biology Cell biology rac GTP-Binding Proteins medicine.anatomical_structure biology.protein Signal transduction |
| Zdroj: | Journal of cell science. 120(Pt 4) |
| ISSN: | 0021-9533 |
| Popis: | Rac1 and Rac3 are highly homologous members of the Rho small GTPase family. Rac1 is ubiquitously expressed and regulates cell adhesion, migration and differentiation in various cell types. Rac3 is primarily expressed in brain and may therefore have a specific function in neuronal cells. We found that depletion of Rac1 by short interference RNA leads to decreased cell-matrix adhesions and cell rounding in neuronal N1E-115 cells. By contrast, depletion of Rac3 induces stronger cell adhesions and dramatically increases the outgrowth of neurite-like protrusions, suggesting opposite functions for Rac1 and Rac3 in neuronal cells. Consistent with this, overexpression of Rac1 induces cell spreading, whereas overexpression of Rac3 results in a contractile round morphology. Rac1 is mainly found at the plasma membrane, whereas Rac3 is predominantly localized in the perinuclear region. Residues 185-187, present in the variable polybasic rich region at the carboxyl terminus are responsible for the difference in phenotype induced by Rac1 and Rac3 as well as for their different intracellular localization. The Rac1-opposing function of Rac3 is not mediated by or dependent on components of the RhoA signaling pathway. It rather seems that Rac3 exerts its function through negatively affecting integrin-mediated cell-matrix adhesions. Together, our data reveal that Rac3 opposes Rac1 in the regulation of cell adhesion and differentiation of neuronal cells. |
| Databáze: | OpenAIRE |
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