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Updated: Feb 2, 2026

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Parallel signaling pathways regulate excitable dynamics differently to mediate pseudopod formation during eukaryotic

Yuki Tanabe1,2, Yoichiro Kamimura3, Masahiro Ueda4,2,5

  • 1Laboratory of Single Molecular Biology, Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan.

Journal of Cell Science
|November 9, 2018
PubMed
Summary

Two signaling pathways in cell movement exhibit distinct refractory periods, influencing pseudopod formation frequency. Soluble guanylyl cyclase (sGC) signaling leads to more frequent responses and pseudopod formation due to its shorter refractory period.

Keywords:
ChemotaxisExcitabilityPseudopod formationcGMP signaling

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Area of Science:

  • Cellular biology
  • Biophysics
  • Biochemistry

Background:

  • Eukaryotic chemotaxis involves parallel signaling pathways regulating cell motility.
  • The distinct excitability and roles of these pathways are not fully understood.
  • Understanding these pathways is crucial for elucidating cell movement mechanisms.

Purpose of the Study:

  • To investigate the differences in excitability and refractory periods of two parallel signaling pathways in eukaryotic chemotaxis.
  • To elucidate the mechanisms underlying pseudopod formation and cyclical motility.
  • To determine how different timescales of pathway response contribute to chemotaxis.

Main Methods:

  • Simultaneous observation of excitable properties of soluble guanylyl cyclase (sGC) and phosphoinositide 3-kinase (PI3K) pathways in *Dictyostelium* cells.
  • Analysis of all-or-none responses for sGC localization and phosphatidylinositol 3,4,5-trisphosphate production.
  • Investigation of regulatory mechanisms for sGC excitability, including feedback loops involving cGMP and GbpC.

Main Results:

  • Both sGC and PI3K pathways showed similar all-or-none responses but differed in their refractory periods.
  • The sGC pathway, with its shorter refractory period, responded more frequently to chemoattractants, resulting in higher pseudopod formation frequency.
  • sGC excitability is negatively regulated by cGMP and GbpC, involving suppression of F-actin polymerization, establishing a delayed negative-feedback mechanism.

Conclusions:

  • Parallel signaling pathways in chemotaxis operate on different timescales, dictated by their intrinsic excitability.
  • The distinct refractory periods of sGC and PI3K pathways allow for differential responses to environmental cues.
  • A delayed negative-feedback mechanism involving sGC, cGMP, and GbpC underlies cyclical pseudopod formation and chemotactic motility.