論文

査読有り
2012年12月

Synthetic spatially graded Rac activation drives cell polarization and movement

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Benjamin Lin
  • ,
  • William R. Holmes
  • ,
  • C. Joanne Wang
  • ,
  • Tasuku Ueno
  • ,
  • Andrew Harwell
  • ,
  • Leah Edelstein-Keshet
  • ,
  • Takanari Inoue
  • ,
  • Andre Levchenko

109
52
開始ページ
E3668
終了ページ
E3677
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1210295109
出版者・発行元
NATL ACAD SCIENCES

Migrating cells possess intracellular gradients of active Rho GTPases, which serve as central hubs in transducing signals from extracellular receptors to cytoskeletal and adhesive machinery. However, it is unknown whether shallow exogenously induced intracellular gradients of Rho GTPases are sufficient to drive cell polarity and motility. Here, we use microfluidic control to generate gradients of a small molecule and thereby directly induce linear gradients of active, endogenous Rac without activation of chemotactic receptors. Gradients as low as 15% were sufficient not only to trigger cell migration up the chemical gradient but to induce both cell polarization and repolarization. Cellular response times were inversely proportional to the steepness of Rac inducer gradient in agreement with a mathematical model, suggesting a function for chemoattractant gradient amplification upstream of Rac. Increases in activated Rac levels beyond a well-defined threshold augmented polarization and decreased sensitivity to the imposed gradient. The threshold was governed by initial cell polarity and PI3K activity, supporting a role for both in defining responsiveness to Rac activation. Our results reveal that Rac can serve as a starting point in defining cell polarity. Furthermore, our methodology may serve as a template to investigate processes regulated by intracellular signaling gradients.

リンク情報
DOI
https://doi.org/10.1073/pnas.1210295109
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000313627700011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1073/pnas.1210295109
  • ISSN : 0027-8424
  • Web of Science ID : WOS:000313627700011

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