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Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Modeling the role of homologous receptor desensitization in cell gradient sensing

Francis Lin1, Eugene C Butcher

  • 1Department of Pathology, Laboratory of Immunology and Vascular Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA. flin2@stanford.edu

Journal of Immunology (Baltimore, Md. : 1950)
|December 4, 2008
PubMed

Insights

Homologous receptor desensitization is crucial for cells to navigate complex chemoattractant fields. This process allows cells to integrate signals and orient towards distant gradients, unlike non-desensitizing receptors.

Area of Science:

  • Cellular Biology
  • Biophysics
  • Chemotaxis Research

Background:

  • G-protein-coupled chemoattractant receptors mediate cell orientation and motility.
  • These receptors desensitize rapidly after ligand binding, but the importance of this desensitization for navigation was unclear.
  • Mutated, non-desensitizable receptors have been shown to support efficient chemotaxis.

Purpose of the Study:

  • To investigate the role of homologous receptor desensitization in cellular navigation within competing chemoattractant fields.
  • To determine if desensitization is necessary for integrating signals and navigating complex environments.
  • To model receptor-mediated orientation and predict cell behavior under different desensitization conditions.

Main Methods:

  • Computational modeling of receptor-mediated cell orientation.
  • Analysis of cell behavior in simulated fields of competing chemoattractants.
  • Comparison of predicted cell navigation with normal vs. non-desensitizable receptors.

Main Results:

  • Modeling predicts that desensitization enables integration of attractant signals, allowing cells to orient to distant gradients.
  • Cells with normal receptors are predicted to seek intermediate positions between balanced attractant sources.
  • Absence of desensitization leads to orientation dominated by local sources, hindering navigation in complex fields.

Conclusions:

  • Homologous receptor desensitization is critical for cellular navigation in complex chemoattractant environments.
  • Desensitization allows cells to effectively integrate signals and navigate away from local dominance.
  • The kinetics of receptor desensitization and recycling influence cell orientation in competing gradients.

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