title: Regulators and Effectors of Arf GTPases in Neutrophils.
abstract: Polymorphonuclear neutrophils (PMNs) are key innate immune cells that represent the first line of defence against infection. They are the first leukocytes to migrate from the blood to injured or infected sites. This process involves molecular mechanisms that coordinate cell polarization, delivery of receptors, and activation of integrins at the leading edge of migrating PMNs. These phagocytes actively engulf microorganisms or form neutrophil extracellular traps (NETs) to trap and kill pathogens with bactericidal compounds. Association of the NADPH oxidase complex at the phagosomal membrane for production of reactive oxygen species (ROS) and delivery of proteolytic enzymes into the phagosome initiate pathogen killing and removal. G protein-dependent signalling pathways tightly control PMN functions. In this review, we will focus on the small monomeric GTPases of the Arf family and their guanine exchange factors (GEFs) and GTPase activating proteins (GAPs) as components of signalling cascades regulating PMN responses. GEFs and GAPs are multidomain proteins that control cellular events in time and space through interaction with other proteins and lipids inside the cells. The number of Arf GAPs identified in PMNs is expanding, and dissecting their functions will provide important insights into the role of these proteins in PMN physiology.
authors.affiliation: Division of Infectious Diseases and Immunology, CHU de Quebec Research Center, Quebec, QC, Canada G1V 4G2.
authors.forename: Jouda
authors.initials: J
authors.lastname: Gamara
authors.affiliation: Division of Infectious Diseases and Immunology, CHU de Quebec Research Center, Quebec, QC, Canada G1V 4G2.
authors.forename: François
authors.initials: F
authors.lastname: Chouinard
authors.affiliation: Division of Infectious Diseases and Immunology, CHU de Quebec Research Center, Quebec, QC, Canada G1V 4G2.
authors.forename: Lynn
authors.initials: L
authors.lastname: Davis
authors.affiliation: Division of Infectious Diseases and Immunology, CHU de Quebec Research Center, Quebec, QC, Canada G1V 4G2 ; Faculty of Medicine, Laval University, Quebec, QC, Canada G1V 0A6.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
authors.affiliation: Division of Infectious Diseases and Immunology, CHU de Quebec Research Center, Quebec, QC, Canada G1V 4G2 ; Faculty of Medicine, Laval University, Quebec, QC, Canada G1V 0A6.
authors.forename: Sylvain G
authors.initials: SG
authors.lastname: Bourgoin
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D017382:Reactive Oxygen Species; D020558:GTP Phosphohydrolases; D020823:ADP-Ribosylation Factor 1