Many mammalian cells can detect and migrate upward in a gradient of chemoattractant.
This process, called chemotaxis, is especially important for neutrophils and other inflammatory cells, which enter sites of inflammation by responding to chemoattractants that bind to GPCRs linked to Gi proteins. These cells are able to migrate upward in a gradient in which chemoattractant at the front of the cell is no more than two percent higher than at the back of the cell. Efforts in many laboratories have identified a number of important chemoattractant receptors and their physiological ligands and are beginning to characterize aspects of the reorganization of the actin cytoskeleton that underlies cell motility. During the past four years we have begun to explore this question. Here we describe experiments designed to assess roles of GPCRs and Gi alpha and beta subunits in mediating chemotaxis, as well as the process that reorganizes the actin cytoskeleton at the leading edge.