A Spatially Restricted Increase in Receptor Mobility Is Involved in Directional Sensing During Dictyostelium Discoideum Chemotaxis

J Cell Sci. 2008 May 15;121(Pt 10):1750-7. doi: 10.1242/jcs.030692.

Abstract

The directed cell migration towards a chemotactic source, chemotaxis, involves three complex and interrelated processes: directional sensing, cell polarization and motility. Directional sensing allows migrating eukaryotic cells to chemotax in extremely shallow gradients (<2% across the cell body) of the chemoattractant. Although directional sensing has been observed as spatially restricted responses along the plasma membrane, our understanding of the ;compass' of the cell that controls the gradient-induced translocation of proteins during chemotactic movements is still largely lacking. Until now, the dynamical behaviour and mobility of the chemoattractant-receptor molecule has been neglected in models describing the directional sensing mechanisms. Here, we show by single-molecule microscopy an agonist-induced increase in the mobile fraction of cAMP-receptor at the leading edge of chemotacting Dictyostelium discoideum cells. The onset of receptor mobility was correlated to the uncoupling and activation of the Galpha2-protein. A finite-element simulation showed that the increase in mobile fraction of the activated receptor enabled the amplified generation of activated Gbetagamma-dimers at the leading edge of the cell, faithfully representing a primary linear amplification step in directional sensing. We propose here that modulation of the receptor mobility is directly involved in directional sensing and provides a new mechanistic basis for the primary amplification step in current theoretical models that describe directional sensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemotactic Factors / metabolism*
  • Chemotaxis / physiology*
  • Dictyostelium / cytology
  • Dictyostelium / physiology*
  • Dimerization
  • GTP-Binding Protein alpha Subunits / metabolism
  • GTP-Binding Protein beta Subunits / metabolism
  • GTP-Binding Protein gamma Subunits / metabolism
  • Protozoan Proteins / metabolism*
  • Receptors, Cyclic AMP / metabolism*
  • Recombinant Fusion Proteins / metabolism

Substances

  • Chemotactic Factors
  • GTP-Binding Protein alpha Subunits
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Protozoan Proteins
  • Receptors, Cyclic AMP
  • Recombinant Fusion Proteins
  • cyclic AMP receptor cAR1