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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Berger, Jürgen Nordheim, Alfred Philippar, Ulrike Schwarz, Heinz Schratt, Gerhard Heidenreich, Olaf |
| Description | Author Affiliation: Schratt G ( Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, 72076 Tübingen, Germany.) |
| Abstract | The activity of serum response factor (SRF), an essential transcription factor in mouse gastrulation, is regulated by changes in actin dynamics. Using Srf(−/−) embryonic stem (ES) cells, we demonstrate that SRF deficiency causes impairments in ES cell spreading, adhesion, and migration. These defects correlate with defective formation of cytoskeletal structures, namely actin stress fibers and focal adhesion (FA) plaques. The FA proteins FA kinase (FAK), β1-integrin, talin, zyxin, and vinculin were downregulated and/or mislocalized in ES cells lacking SRF, leading to inefficient activation of the FA signaling kinase FAK. Reduced overall actin expression levels in Srf(−/−) ES cells were accompanied by an offset treadmilling equilibrium, resulting in lowered F-actin levels. Expression of active RhoA-V14 rescued F-actin synthesis but not stress fiber formation. Introduction of constitutively active SRF-VP16 into Srf(−/−) ES cells, on the other hand, strongly induced expression of FA components and F-actin synthesis, leading to a dramatic reorganization of actin filaments into stress fibers and lamellipodia. Thus, using ES cell genetics, we demonstrate for the first time the importance of SRF for the formation of actin-directed cytoskeletal structures that determine cell spreading, adhesion, and migration. Our findings suggest an involvement of SRF in cell migratory processes in multicellular organisms. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 4 |
| Volume Number | 156 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2002-02-18 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Actins Metabolism Cytoskeleton Physiology Focal Adhesions Serum Response Factor Genetics Animals Antigens, CD29 Cell Adhesion Cell Movement Enzyme Activation Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gene Expression Regulation Herpes Simplex Virus Protein Vmw65 Metalloproteins Mice Mice, Knockout Protein-Tyrosine Kinases Recombinant Fusion Proteins Stem Cells Cytology Talin Vinculin Zyxin RhoA GTP-Binding Protein Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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