Rhodocetin-αβ-induced neuropilin-1-cMet association triggers restructuring of matrix contacts in endothelial cells

• Verfasst von: Niland, Stephan [VerfasserIn]
• Verfasst von: Ditkowski, Bartosz [VerfasserIn]
• Verfasst von: Parrandier, Désirée [VerfasserIn]
• Verfasst von: Roth, Lise [VerfasserIn]
• Verfasst von: Augustin, Hellmut [VerfasserIn]
• Verfasst von: Eble, Johannes A. [VerfasserIn]
• Titel: Rhodocetin-αβ-induced neuropilin-1-cMet association triggers restructuring of matrix contacts in endothelial cells
• Verf.angabe: Stephan Niland, Bartosz Ditkowski, Désirée Parrandier, Lise Roth, Hellmut Augustin, and Johannes A. Eble
• E-Jahr: 2013
• Jahr: 3 Jan 2013
• Fussnoten: Gesehen am 26.01.2022
• Titel Quelle: Enthalten in: Arteriosclerosis, thrombosis, and vascular biology
• Ort Quelle: Philadelphia, Pa. : Lippincott, Williams & Wilkins, 1981
• Jahr Quelle: 2013
• Band/Heft Quelle: 33(2013), 3, Seite 544-554
• ISSN Quelle: 1524-4636
• ISSN Quelle: 2330-9180
• ISSN Quelle: 2330-9199
• DOI: doi:10.1161/ATVBAHA.112.00006
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Erscheint auch als : Druck-Ausgabe: Niland, Stephan, 1964 - : Rhodocetin-αβ-induced neuropilin-1-cMet association triggers restructuring of matrix contacts in endothelial cells. - 2013
• Sach-SW: adhesome
• Sach-SW: endothelial cell
• Sach-SW: force management
• Sach-SW: neuropilin-1
• Sach-SW: rhodocetin
• K10plus-PPN: 1787207862

Abstract

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.