α4β1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation

Dustin A. Dikeman, Leslie A. Rivera Rosado, Troy A. Horn, Christina S. Alves, K Konstantopoulos, Joy T. Yang

Research output: Contribution to journalArticle

Abstract

α4β1-Integrin plays a pivotal role in cell migration in vivo. This integrin has been shown to regulate the front-back polarity of migrating cells via localized inhibition of α4- integrin/paxillin binding by phosphorylation at the α4-integrin cytoplasmic tail. Here, we demonstrate that α4β 1-integrin regulates directionally persistent cell migration via a more complex mechanism in which α4-integrin phosphorylation and paxillin binding act via both cooperative and independent pathways. We show that, in response to shear flow, α4β1-integrin binding to the CS-1 region of fibronectin was necessary and sufficient to promote directionally persistent cell migration when this integrin was ectopically expressed in CHO cells. Under shear flow, the α 4β1-integrin-expressing cells formed a fan shape with broad lamellipodia at the front and retracted trailing edges at the back. This "fanning" activity was enhanced by disrupting paxillin binding alone and inhibited by disrupting phosphorylation alone or together with disrupting paxillin binding. Notably, the phosphorylation-disrupting mutation and the double mutation resulted in the formation of long trailing tails, suggesting that α4-integrin phosphorylation is required for trailing edge retraction/detachment independent of paxillin binding. Furthermore, the stable polarity and directional persistence of shear flow-stimulated cells were perturbed by the double mutation but not the single mutations alone, indicating that paxillin binding and α4-integrin phosphorylation can facilitate directionally persistent cell migration in an independent and compensatory manner. These findings provide a new insight into the mechanism by which integrins regulate directionally persistent cell migration.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume295
Issue number1
DOIs
StatePublished - Jul 2008

Fingerprint

Integrins
Cell Movement
Paxillin
Phosphorylation
Mutation
Cell Polarity
Pseudopodia
CHO Cells

Keywords

  • Fibronectin
  • Lamellipodia
  • Shear stress

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

α4β1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation. / Dikeman, Dustin A.; Rivera Rosado, Leslie A.; Horn, Troy A.; Alves, Christina S.; Konstantopoulos, K; Yang, Joy T.

In: American Journal of Physiology - Cell Physiology, Vol. 295, No. 1, 07.2008.

Research output: Contribution to journalArticle

Dikeman, Dustin A. ; Rivera Rosado, Leslie A. ; Horn, Troy A. ; Alves, Christina S. ; Konstantopoulos, K ; Yang, Joy T. / α4β1-Integrin regulates directionally persistent cell migration in response to shear flow stimulation. In: American Journal of Physiology - Cell Physiology. 2008 ; Vol. 295, No. 1.
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