Rhodocetin-αβ-induced neuropilin-1-cMet association triggers restructuring of matrix contacts in endothelial cells
Objective— - - The snake venom component rhodocetin-αβ (RCαβ) stimulates endothelial cell motility in an α2β1 integrin-independent manner. We aimed to elucidate its cellular and molecular mechanisms. - - Methods and Results— - - We identified neuropilin-1 (Nrp1) as a novel target of RCαβ by prote...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
3 Jan 2013
|
| In: |
Arteriosclerosis, thrombosis, and vascular biology
Year: 2013, Volume: 33, Issue: 3, Pages: 544-554 |
| ISSN: | 1524-4636 |
| DOI: | 10.1161/ATVBAHA.112.00006 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1161/ATVBAHA.112.00006 Verlag, kostenfrei, Volltext: https://www.ahajournals.org/doi/10.1161/ATVBAHA.112.00006 
|
| Author Notes: | Stephan Niland, Bartosz Ditkowski, Désirée Parrandier, Lise Roth, Hellmut Augustin, and Johannes A. Eble |
| Summary: | Objective— - - The snake venom component rhodocetin-αβ (RCαβ) stimulates endothelial cell motility in an α2β1 integrin-independent manner. We aimed to elucidate its cellular and molecular mechanisms. - - Methods and Results— - - We identified neuropilin-1 (Nrp1) as a novel target of RCαβ by protein-chemical methods. RCαβ and vascular endothelial growth factor (VEGF)-A avidly bind to Nrp1. Instead of acting as VEGF receptor 2 coreceptor, Nrp1 associates upon RCαβ treatment with cMet. Furthermore, cell-based ELISAs and kinase inhibitor studies showed that RCαβ induces phosphorylation of tyrosines 1234/1235 and thus activation of cMet. Consequently, paxillin is phosphorylated at Y31, which is redistributed from streak-like focal adhesions to spot-like focal contacts at the cell perimeter, along with α2β1 integrin, thereby regulating cell-matrix interactions. Cortactin is abundant in the cell perimeter, where it is involved in the branching of the cortical actin network of lamellipodia, whereas tensile force-bearing actin stress fibers radiating from focal adhesions disappear together with zyxin, a focal adhesion marker, on RCαβ treatment. - - Conclusion— - - Our data demonstrate that (1) Nrp1 is a novel target for venom components, such as RCαβ; (2) Nrp1 coupled to cMet regulates the type of cell-matrix interactions in a manner involving paxillin phosphorylation; and (3) altered cell-matrix interactions determine endothelial cell migration and cellular force management. |
|---|---|
| Item Description: | Gesehen am 26.01.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1524-4636 |
| DOI: | 10.1161/ATVBAHA.112.00006 |