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| Content Provider | Springer Nature Link |
|---|---|
| Author | Schnittler, Hans Joachim Schneider, Stefan W. Raifer, Hartmann Luo, Fei Dieterich, Peter Just, Ingo Aktories, Klaus |
| Copyright Year | 2001 |
| Abstract | Clostridium botulinum C2 toxin (C2 toxin) and purified ADP-ribosylated-α-actin (ADP-r-α-actin) cause specific actin depolymerisation in living cells. This effect was used to investigate the actin microfilament system with particular emphasis on cell-cell adhesion and plasma membrane integrity in endothelial cells. C2 toxin caused time- and dose-dependent (15–100 ng/ml) changes in endothelial surface morphology (investigated by atomic force microscopy), intercellular gap formation and cell detachment under shear stress. Low concentrations of C2 toxin (1.5 ng/ml), however, did not induce cell detachment but inhibited shear stress-dependent cell alignment. Gap formation as well as cell loss under shear stress was also observed in cells microinjected with purified ADP-r-α-actin. Intercellular gap formation was mediated by increased α-catenin solubility (40%) due to actin filament depolymerisation. Disintegration of plasma membranes (measured by LDH release) and cell fragmentation during simultaneous exposure to shear stress and C2 toxin were due to a loss of more than 50% of membrane-associated actin. These data show that small disturbances in actin dynamics inhibit shear stress-dependent cell alignment; that depolymerisation of actin filaments increases the solubility of α-catenin, thus resulting in cell dissociation and that actin filaments of the membrane cytoskeleton are required to protect the cells from haemodynamic injury such as shear stress. Together, the study shows a heterogeneous regulation of actin filament dynamics at subcellular locations. Junction-associated actin filaments displayed the highest sensitivity whereas stress fibres were far more stable. |
| Starting Page | 675 |
| Ending Page | 687 |
| Page Count | 13 |
| File Format | |
| ISSN | 00316768 |
| Journal | Pflügers Archiv |
| Volume Number | 442 |
| Issue Number | 5 |
| e-ISSN | 14322013 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2001-05-19 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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