Changes in cholesterol levels in the plasma membrane modulate cell signaling and regulate cell adhesion and migration on fibronectin
| Autor: | K. Sridhar Rao, Gopal Pande, Jean Paul Thiery, O. G. Ramprasad, G. Srinivas, Sylvie Dufour, Powrnima Joshi |
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| Rok vydání: | 2007 |
| Předmět: |
Integrin
macromolecular substances Focal adhesion Cell membrane Mice Cell Movement Structural Biology Cell Line Tumor Cell Adhesion medicine Animals Humans Phosphorylation Cell adhesion Cytoskeleton Paxillin biology Cell adhesion molecule Cell Membrane Cell Biology Actin cytoskeleton Actins Fibronectins Cell biology Enzyme Activation Fibronectin Protein Transport Cholesterol medicine.anatomical_structure Focal Adhesion Protein-Tyrosine Kinases biology.protein Mitogen-Activated Protein Kinases Integrin alpha5beta1 Signal Transduction |
| Zdroj: | Cell Motility and the Cytoskeleton. 64:199-216 |
| ISSN: | 1097-0169 0886-1544 |
| Popis: | The number and distribution of lipid molecules, including cholesterol in particular, in the plasma membrane, may play a key role in regulating several physiological processes in cells. We investigated the role of membrane cholesterol in regulating cell shape, adhesion and motility. The acute depletion of cholesterol from the plasma membrane of cells that were well spread and motile on fibronectin caused the rounding of these cells and decreased their adhesion to and motility on fibronectin. These modifications were less pronounced in cells plated on laminin, vitronectin or plastic, indicating that cholesterol-mediated changes in adhesion and motility are more specific for adhesion mediated by fibronectin-specific integrins, such as alpha5beta1. These changes were accompanied by remodeling of the actin cytoskeleton, the spatial reorganization of paxillin in the membrane, and changes to the dynamics of alpha5 integrin and paxillin-rich focal adhesions. Levels of tyrosine phosphorylation at position 576/577 of FAK and Erk1/Erk2 MAP-kinase activity levels were both lower in cholesterol-depleted than in control cells. These levels normalized only on fibronectin when cholesterol was reincorporated into the cell membrane. Thus, membrane cholesterol content has a specific effect on certain signaling pathways specifically involved in regulating cell motility on fibronectin and organization of the actin cytoskeleton. |
| Databáze: | OpenAIRE |
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