Activation of endogenous Cdc42 visualized in living cells

Science. 2004 Sep 10;305(5690):1615-9. doi: 10.1126/science.1100367.

Abstract

Signaling proteins are tightly regulated spatially and temporally to perform multiple functions. For Cdc42 and other guanosine triphosphatases, the subcellular location of activation is a critical determinant of cell behavior. However, current approaches are limited in their ability to examine the dynamics of Cdc42 activity in living cells. We report the development of a biosensor capable of visualizing the changing activation of endogenous, unlabeled Cdc42 in living cells. With the use of a dye that reports protein interactions, the biosensor revealed localized activation in the trans-Golgi apparatus, microtubule-dependent Cdc42 activation at the cell periphery, and activation kinetics precisely coordinated with cell extension and retraction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Algorithms
  • Animals
  • Biosensing Techniques*
  • Cell Adhesion
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Polarity
  • Cell Surface Extensions / metabolism
  • Cell Surface Extensions / ultrastructure
  • Endothelial Cells / metabolism
  • Endothelial Cells / ultrastructure
  • Fibroblasts
  • Fluorescence
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Proteins
  • Mice
  • Microtubules / metabolism
  • Neutrophil Activation
  • Neutrophils / metabolism*
  • Proteins / chemistry
  • Proteins / metabolism
  • Pseudopodia / metabolism
  • Pyrimidinones / metabolism
  • Sensitivity and Specificity
  • Wiskott-Aldrich Syndrome Protein
  • cdc42 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins / metabolism
  • trans-Golgi Network / metabolism*
  • trans-Golgi Network / ultrastructure

Substances

  • Actins
  • Fluorescent Dyes
  • Luminescent Proteins
  • Proteins
  • Pyrimidinones
  • WAS protein, human
  • Was protein, mouse
  • Wiskott-Aldrich Syndrome Protein
  • Green Fluorescent Proteins
  • merocyanine dye
  • RHOQ protein, human
  • Rhoq protein, mouse
  • cdc42 GTP-Binding Protein
  • rho GTP-Binding Proteins