Abstract
Rac‐GTPases and their Rac‐GEF activators play important roles in the recruitment and host defence functions of neutrophils. These proteins control the activation of adhesion molecules and the cytoskeletal dynamics that enable the adhesion, migration and tissue recruitment of neutrophils. They also regulate the effector functions that allow neutrophils to kill bacterial and fungal pathogens, and to clear debris. This review focuses on the roles of Rac‐GTPases and Rac‐GEFs in neutrophil adhesion, migration and recruitment.
Highlights
Rac-GTPases and their Rac-guaninenucleotide exchange factors (GEFs) activators play important roles in the recruitment and host defence functions of neutrophils
Under flow conditions, Prex1À/À neutrophils show impaired slow rolling, due to effects on E-selectin-mediated activation of the b2integrin LFA-1, as well as reduced Mac-1 integrindependent crawling on endothelial cells.[55]
As active RhoG is an upstream regulator of DOCK2, P-Rex[1] might signal through RhoG to activate DOCK2.30 as described above, the actin polymerization and migration defects of Prex1À/À and Dock2À/ Àneutrophils are more varied and severe than those of RhoGÀ/À neutrophils, which implies that these GEFs signal largely independently of RhoG and each other to generate neutrophil responses
Summary
Rac proteins are small guanine-nucleotide binding proteins (G proteins, GTPases) of the Rho family.[11,12] Neutrophils express the ubiquitous isoform Rac[1], hematopoietic Rac[2] and widely expressed RhoG, but not the neuronal isoform Rac3.13 These GTPases control the structure of the actomyosin cytoskeleton by signalling through several pathways, mainly through IRSp53, WAVE and Arp2/3, enabling the polymerization of branched actin filaments at the cell periphery. These mechanisms determine which Rac-dependent cell responses ensue.[13,20] CIRCULATING NEUTROPHIL
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