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Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
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A PIP5 kinase essential for efficient chemotactic signaling.
Louise Fets1, John M E Nichols1, Robert R Kay1
1Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Current Biology : CB
|February 4, 2014
Summary
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial for directed cell migration in Dictyostelium. The enzyme PikI regulates PI(4,5)P2 levels, impacting gradient sensing and downstream signaling pathways.
Area of Science:
- Cell biology
- Biochemistry
- Molecular biology
Background:
- Chemoattractant gradients guide cell migration through signaling events.
- Phosphoinositides, like PI(3,4,5)P3, are key regulators of chemotaxis.
- The role of PI(4,5)P2 in cell migration is not well understood.
Purpose of the Study:
- To investigate the role of PikI, a PIP5 kinase, in Dictyostelium chemotaxis.
- To determine the impact of PikI on PI(4,5)P2 levels and cell behavior.
- To elucidate the relationship between PikI, PI(4,5)P2, and downstream signaling.
Main Methods:
- Characterization of a PIP5 kinase, PikI, in Dictyostelium.
- Quantification of PI(4,5)P2 levels in wild-type and pikI(-) cells.
- Analysis of cell migration, speed, and orientation in response to cAMP gradients.
- Investigation of Ras and PKB activation in pikI(-) cells.
Main Results:
- PikI is essential for efficient Dictyostelium chemotaxis.
- PikI deficiency reduces PI(4,5)P2 levels by 90% and causes disorientation in cAMP gradients.
- Ras activation is normal in pikI(-) cells, but Ras-dependent responses are impaired.
- PKB phosphorylation of PikI enhances its activity.
Conclusions:
- Adequate PI(4,5)P2 levels, regulated by PikI, are necessary for coupling Ras to downstream effectors.
- PikI is a critical component of the gradient sensing machinery in Dictyostelium.
- PikI represents a novel regulatory point in chemotaxis signaling.
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