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Sci. STKE, 5 August 2003
[DOI: 10.1126/stke.2003.194.cm1]

CONNECTIONS MAP OVERVIEWS

Dictyostelium discoideum cAMP Chemotaxis Pathway

Alan R. Kimmel1 and Carole A. Parent2*

1Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract: Cells migrating directionally toward a chemoattractant display highly polarized cytoskeletal organizations, with F-actin predominantly at the anterior and myosin II localized laterally and posteriorly. Dictyostelium discoideum has proven a remarkable model system for elucidating signaling pathways that regulate this chemotactic response. During development, extracellular adenosine 3',5'-monophosphate (cAMP) functions as a primary signal to activate a specific family of heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled, seven-transmembrane receptors and their downstream effectors, phospholipase C (PLC), adenylyl cyclase (AC), phosphatidylinositol 3-kinase (PI3K), the lipid phosphatase PTEN, and guanylyl cyclase (GC). The PI3K-PTEN and GC pathways interact to establish polarity in chemotaxing D. discoideum. Receptor-mediated signaling spatially restricts PI3K and PTEN localization; this directs phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] to the anterior of the cell, thus recruiting a family of pleckstrin homology (PH) domain-containing proteins. These and other signaling components ultimately localize F-actin. Data suggest that guanosine 3',5'-monophosphate (cGMP) target proteins and p21-activated kinase (PAKa) cooperate to regulate the phosphorylation state and assembly of myosin II. Many of the molecular interactions described in the Connections Map are fundamental to regulating chemotaxis in all eukaryotic cells.

Science Viewpoint

A. R. Kimmel, C. A. Parent, The signal to move: D. discoideum go orienteering. Science 300, 1525-1527 (2003). [Abstract] [Full Text]

*Corresponding author. E-mail, parentc{at}helix.nih.gov

Citation: A. R. Kimmel, C. A. Parent, Dictyostelium discoideum cAMP Chemotaxis Pathway. Sci. STKE 2003, cm1 (2003).

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