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

J Cell Biol. 2017 Nov 6;216(11):3785-3798. doi: 10.1083/jcb.201701176. Epub 2017 Sep 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Adhesion*
  • Cell Line
  • Cell Shape*
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Fibroblasts / metabolism*
  • Genotype
  • Mice, Knockout
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Paxillin / genetics
  • Paxillin / metabolism*
  • Phenotype
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Pseudopodia / metabolism*
  • Signal Transduction
  • Talin / deficiency
  • Talin / genetics
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Muscle Proteins
  • Neuropeptides
  • Paxillin
  • Pxn protein, mouse
  • Rac1 protein, mouse
  • Talin
  • kindlin-1 protein, mouse
  • kindlin-2 protein, mouse
  • talin protein, mouse
  • rac1 GTP-Binding Protein

Associated data

  • PDB/4CYE
  • PDB/3IVF