Abstract
Chemotaxis, or directional movement towards an extracellular gradient of chemicals, is necessary for processes as diverse as finding nutrients, the immune response, metastasis and wound healing. Activation of G-protein coupled receptors (GPCRs) is at the very base of the chemotactic signaling pathway. Chemotaxis starts with binding of the chemoattractant to GPCRs at the cell-surface, which finally leads to major changes in the cytoskeleton and directional cell movement towards the chemoattractant. Many chemotaxis pathways that are directly regulated by Gβγ have been identified and studied extensively; however, whether Gα is just a handle that regulates the release of Gβγ or whether Gα has its own set of distinct chemotactic effectors, is only beginning to be understood. In this review, we will discuss the different levels of regulation in GPCR signaling and the downstream pathways that are essential for proper chemotaxis.
Highlights
Chemotaxis, the process of directed cell movement towards a chemical gradient, plays an important role in both prokaryotes and eukaryotes
Chemotaxis is essential for the Dictyostelium life cycle: during the vegetative phase of their life cycle, Dictyostelium scavenges the soil for bacteria by chemotaxing towards folic acid released by bacteria; if food is scarce, Dictyostelium cells secrete cyclic AMP, which is used as a chemoattractant by neighboring cells to form a multicellular structure with spores that can resist harsh conditions
Our work has shown that Dictyostelium Ric8 serves as a non-receptor GEF that is important for development and chemotaxis to cyclic AMP (cAMP) and folate [50]
Summary
Chemotaxis, the process of directed cell movement towards a chemical gradient, plays an important role in both prokaryotes and eukaryotes. Having clearly distinct physiological roles, Dictyostelium and neutrophils have a highly similar chemotactic behavior. They display strong chemotactic responses, their stimuli are well-defined and their chemotaxis is characterized by amoeboid migration, creating actin-rich pseudopods at the front and retracting the back of the cell using myosin filaments [3,5]. Chemotaxis starts with binding of the chemoattractant to GPCRs at the cell surface The receptors transmit these signals into the interior of the cell by activation and dissociation of the heterotrimeric G protein complex. We highlight the crucial role of regulators of GPCR and heterotrimeric G-protein signaling and discuss the heterotrimeric pathways regulating chemotaxis
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