Chapter 227 - βγ Signaling in Chemotaxis

Abstract

This chapter discusses the role of G proteins in chemotaxis of Dictyostelium discoideum and neutrophils, with an emphasis on the possible role of proteins involved in lipid production and degradation. Chemotaxis, the ability of a cell to sense and move up a chemical gradient, is important in various physiological processes and is involved in many disease states. Signal transduction during chemotaxis occurs through seven-transmembrane receptors that are coupled to heterotrimeric G proteins. The βγ subunits transmit the signal downstream, and although the direct effectors are unclear, increases in phosphoinositide 3,4,5-trisphosphate and phosphatidylinositide 3,4-bisphosphate occur at the leading edge of the migrating cell. The formation of these lipids results in the recruitment of a variety of signaling proteins. Recent work has implicated phosphatidylinositol 3-kinase and the lipid phosphatases, PTEN, and SHIP in chemotaxis. Directed movement of cells toward soluble attractants (chemotaxis) is critical in immunity, wound healing, embryogenesis, and neuron guidance. Also, abnormalities in chemotaxis have been implicated in disease states such as tumor metastasis, atherosclerosis, arthritis, asthma, and multiple sclerosis. The cell biology of chemotaxis has primarily been studied in two cell types, the social amoeba Dictyostelium discoideum and mammalian leukocytes. Due to the genetic manipulations available, D. discoideum is an excellent model system in which to study chemotactic signaling. Many observations originally made in these simple eukaryotic cells have subsequently held true in mammalian cells such as neutrophils.