The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge

Yuan He, Ashish Kapoor, Sara Cook, Shubai Liu, Yang Kevin Xiang, Christopher V. Rao, Paul J A Kenis, Fei Wang

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Establishing new adhesions at the extended leading edges of motile cells is essential for stable polarity and persistent motility. Despite recent identification of signaling pathways that mediate polarity and chemotaxis in neutrophils, little is known about molecular mechanisms governing cell-extracellular-matrix (ECM) adhesion in these highly polarized and rapidly migrating cells. Here, we describe a signaling pathway in neutrophils that is essential for localized integrin activation, leading edge attachment and persistent migration during chemotaxis. This pathway depends upon G i-protein-mediated activation and leading edge recruitment of Lyn, a nonreceptor tyrosine kinase belonging to the Src kinase family. We identified the small GTPase Rap1 as a major downstream effector of Lyn to regulate neutrophil adhesion during chemotaxis. Depletion of Lyn in neutrophil-like HL-60 cells prevented chemoattractantinduced Rap1 activation at the leading edge of the cell, whereas ectopic expression of Rap1 largely rescued the defects induced by Lyn depletion. Furthermore, Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge. Together, these results provide novel mechanistic insights into the poorly understood signaling network that controls leading edge adhesion during chemotaxis of neutrophils, and possibly other amoeboid cells.

Original languageEnglish (US)
Pages (from-to)2153-2164
Number of pages12
JournalJournal of Cell Science
Volume124
Issue number13
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Keywords

  • Adhesion
  • CrkL
  • Lyn
  • Neutrophil chemotaxis
  • Rap1

ASJC Scopus subject areas

  • Cell Biology

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