Temporal dissection of β1-integrin signaling indicates a role for p130CAS-Crk in filopodia formation

Anna Gustavsson, Ming Yuan, Maria Fällman

Research output: Contribution to journalArticlepeer-review

Abstract

Invasin-promoted spreading of β1-integrin-deficient cells, transfected with the β1A- or β1B-integrin splice variants, were used to dissect early β1-integrin signaling events. The β1B isoform, which has a different membrane-distal part of the cytoplasmic tail from β1A, is defective in signaling and function. When plated on surfaces coated with the high affinity ligand invasin, β1B-integrin-expressing cells spread by forming filopodia with distinct adhesive phosphotyrosine complexes at the tips, without signs of lamellipodia. This suggested that the β 1B-integrin mediated a partial signaling sufficient for formation of filopodia but insufficient for lamellipodia formation. When screening for proteins present in the distal filopodial phosphotyrosine complexes of β1B cells, p130Cas and the filopodia proteins vasodilator-stimulated phosphoprotein and talin were found, whereas the typical focal complex proteins focal adhesion kinase, paxillin, and vinculin were not. Invasin-promoted adhesion induced complex formation of p130Cas and the adapter Crk. Moreover, Crk together with Dock180 were present at the filopodial tips of β1B-integrin-expressing cells, and there was a prominent Rac1 activation. Expression of dominant negative variants of p130Cas or CrkII blocked β1B-integrin-mediated filopodia formation, indicating that this signaling scaffold is central in this process.

Original languageEnglish (US)
Pages (from-to)22893-22901
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number22
DOIs
StatePublished - May 28 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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