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Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis
Lingfeng Chen1, Miho Iijima, Ming Tang
1Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Developmental Cell
|April 11, 2007
Summary
Phospholipase A(2) (PLA(2)) and phosphatidylinositol 3-kinase (PI3K) signaling pathways work together to guide cell movement. PLA(2) metabolites are crucial for cell chemotaxis, complementing PI3K activity.
Area of Science:
- Cellular biology
- Biochemistry
- Molecular biology
Background:
- Directed cell migration is essential for development and immunity.
- Phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P(3)) accumulation is a key signaling event in cell migration.
- Redundant signaling pathways contribute to robust chemotaxis.
Purpose of the Study:
- To identify novel genes and pathways involved in directed cell migration.
- To elucidate the relationship between phospholipase A(2) (PLA(2)) and PI3K signaling in chemotaxis.
Main Methods:
- Genetic screening in Dictyostelium discoideum.
- Gene deletion and analysis of signaling pathway mutants.
- Measurement of PI(3,4,5)P(3) levels and actin polymerization.
- Analysis of arachidonic acid derivative production.
Main Results:
- A PLA(2) homolog was identified as a redundant pathway in chemotaxis.
- PLA(2) and PI3K signaling act in concert; loss of one pathway increases dependence on the other.
- Combined deletion of PLA(2) and PI3K severely impairs chemotaxis and actin polymerization.
- Chemoattractants stimulate PLA(2)-dependent arachidonic acid derivative production.
Conclusions:
- PLA(2) and PI3K signaling pathways are parallel and cooperative in mediating directed cell migration.
- Metabolites produced by PLA(2) signaling are important mediators of chemotaxis.
- This study reveals a novel role for PLA(2) in cell migration beyond PI(3,4,5)P(3) regulation.
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