Connections Map Overview

Dictyostelium discoideum cAMP Chemotaxis Pathway

STKE  05 Aug 2003:
Vol. 2003, Issue 194, pp. cm1
DOI: 10.1126/stke.2003.194.cm1

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]