Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading

Böttcher, Ralph T.; Veelders, Maik; Rombaut, Pascaline; Faix, Jan; Theodosiou, Marina; Stradal, Theresa E.; Rottner, Klemens; Zent, Roy; Herzog, Franz und Faessler, Reinhard (2017): Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading. In: Journal of Cell Biology, Bd. 216, Nr. 11: S. 3785-3798

Abstract

Cell spreading requires the coupling of actin-driven membrane protrusion and integrin-mediated adhesion to the extracellular matrix. The integrin-activating adaptor protein kindlin-2 plays a central role for cell adhesion and membrane protrusion by directly binding and recruiting paxillin to nascent adhesions. Here, we report that kindlin-2 has a dual role during initial cell spreading: it binds paxillin via the pleckstrin homology and F0 domains to activate Rac1, and it directly associates with the Arp2/3 complex to induce Rac1-mediated membrane protrusions. Consistently, abrogation of kindlin-2 binding to Arp2/3 impairs lamellipodia formation and cell spreading. Our findings identify kindlin-2 as a key protein that couples cell adhesion by activating integrins and the induction of membrane protrusions by activating Rac1 and supplying Rac1 with the Arp2/3 complex.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0021-9525
• Sprache: Englisch