Finding the Way: Directional Sensing and Cell Polarization through Ras Signalling

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Atsuo T. Sasaki1 and
  2. Richard A. Firtel2,*

Published Online: 7 OCT 2008

DOI: 10.1002/047001766X.ch8

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

How to Cite

Sasaki, A. T. and Firtel, R. A. (2005) Finding the Way: Directional Sensing and Cell Polarization through Ras Signalling, in Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/047001766X.ch8

Author Information

  1. 1

    Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, 3801 CA 92093, USA

  2. 2

    Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, 0380, University of California, San Diego, 9500 Gilman Drive, La Jolla, 3801 CA 92093–0380, USA

*Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, 0380, University of California, San Diego, 9500 Gilman Drive, La Jolla, 3801 CA 92093–0380, USA

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 9 SEP 2005

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470011904

Online ISBN: 9780470017661

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Keywords:

  • directional cell movement;
  • amoeboid crawling system;
  • cell migration;
  • G protein-coupled receptors (GPCRs);
  • ‘cellular compass’;
  • PTEN;
  • PI3K localization;
  • heterotrimeric G protein-based signalling pathways;
  • Ras activation

Summary

Chemotactic eukaryotic cells have the unique ability to sense a shallow extracellular chemoattractant gradient and translate it into a steep intracellular gradient. For example, phosphoinositide-3,4,5-trisphosphate (PIP3), the product of phosphatidylinositol-3-kinase (PI3K), is accumulated at the leading edge but not the back of a polarized chemotaxing cell. This is partially controlled by the reciprocal, preferential localization of PI3K and PTEN to the membrane at the front and back, respectively. However, upstream events that control the localized activation and localization of PI3K and PTEN remain unclear. Recent findings indicate that Ras is important for activation of the PI3K pathway and regulation of directed cell movement and cell polarity. Ras is activated at the leading edge, and this local activation occurs without asymmetric localization of PI3K and PTEN or the F-actin cytoskeleton. In contrast, PI3K localization is driven by F-actin polymerization. Thus, Ras functions as an essential part of the cell's compass acting upstream of PI3K while reciprocal localization of PI3K and PTEN amplify the PIP3 gradient, rather than create it. These observations suggest a positive feedback loop to amplify an initial PIP3 gradient in which localized F-actin polymerization recruits cytosolic PI3K to the leading edge, where it is activated by Ras to locally produce PIP3 that induces F-actin polymerization.