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Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium

Margarethakay Scavello1, Alexandra R Petlick1, Ramya Ramesh1

  • 1Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721-0088, USA.

Journal of Cell Science
|March 18, 2017
PubMed

Insights

Protein kinase A (PKA) is crucial for directed cell migration in Dictyostelium discoideum. PKA regulates chemoattractant signaling by modulating RasG, Rap1, and TORC2 pathways, ensuring proper chemotaxis.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Developmental biology

Background:

  • Efficient directed cell migration relies on precise spatial and temporal regulation of chemoattractant signal transduction pathways.
  • The precise mechanisms governing this regulation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of protein kinase A (PKA) in regulating chemoattractant (cAMP) signaling in Dictyostelium discoideum.
  • To elucidate how PKA influences chemotaxis and directional sensing.

Main Methods:

  • Utilized Dictyostelium discoideum strains lacking PKA.
  • Employed exogenously expressed cAMP receptor cAR1.
  • Used cells lacking adenylyl cyclase A (ACA).
  • Applied the PKA-selective inhibitor H89.

Main Results:

  • Cells lacking PKA exhibited significant chemotaxis defects and impaired directional sensing.
  • PKA was found to regulate chemoattractant signal transduction via RasG, Rap1, and TORC2 pathways.
  • These pathways lie upstream of PKA and control intracellular cAMP production.

Conclusions:

  • PKA plays a critical role in controlling chemoattractant signal transduction during Dictyostelium chemotaxis.
  • PKA-mediated regulation of RasG, Rap1, and TORC2 constitutes a negative feedback mechanism.
  • This feedback loop is essential for fine-tuning chemoattractant signaling for efficient cell migration.
Keywords:
Chemotactic signalingChemotaxisDirectional sensingMigrationNegative feedbackPKA

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