The Rho Guanine Nucleotide Exchange Factor Syx Regulates the Balance of Dia and ROCK Activities To Promote Polarized-Cancer-Cell Migration
| Autor: | Siu P. Ngok, Laura J. Lewis-Tuffin, Lauren Johnston, Ryan W. Feathers, Rory Geyer, Panos Z. Anastasiadis, Antonis Kourtidis, Justus C. Dachsel |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
RHOA
Formins Microtubules Cell membrane Focal adhesion Cell Movement Cell Line Tumor Cell polarity medicine Guanine Nucleotide Exchange Factors Humans RNA Small Interfering Molecular Biology Cell Shape Actin Adaptor Proteins Signal Transducing Focal Adhesions rho-Associated Kinases biology Protein Stability Cell Polarity Cell migration Cell Biology Articles Cell biology Protein Transport medicine.anatomical_structure Phenotype Gene Knockdown Techniques biology.protein Guanine nucleotide exchange factor |
| Popis: | The role of RhoA in promoting directed cell migration has been complicated by studies showing that it is activated both in the front and the rear of migrating cells. We report here that the RhoA-specific guanine nucleotide exchange factor Syx is required for the polarity of actively migrating brain and breast tumor cells. This function of Syx is mediated by the selective activation of the RhoA downstream effector Dia1, the subsequent reorganization of microtubules, and the downregulation of focal adhesions and actin stress fibers. The data argue that directed cell migration requires the precise spatiotemporal regulation of Dia1 and ROCK activities in the cell. The recruitment of Syx to the cell membrane and the subsequent selective activation of Dia1 signaling, coupled with the suppression of ROCK and activation of cofilin-mediated actin reorganization, plays a key role in establishing cell polarity during directed cell migration. |
| Databáze: | OpenAIRE |
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