title: ARHGAP25, a novel Rac GTPase-activating protein, regulates phagocytosis in human neutrophilic granulocytes.
abstract: Members of the Rac/Rho family of small GTPases play an essential role in phagocytic cells in organization of the actin cytoskeleton and production of toxic oxygen compounds. GTPase-activating proteins (GAPs) decrease the amount of the GTP-bound active form of small GTPases, and contribute to the control of biologic signals. The number of potential Rac/RhoGAPs largely exceeds the number of Rac/Rho GTPases and the expression profile, and their specific role in different cell types is largely unknown. In this study, we report for the first time the properties of full-length ARHGAP25 protein, and show that it is specifically expressed in hematopoietic cells, and acts as a RacGAP both in vitro and in vivo. By silencing and overexpressing the protein in neutrophil model cell lines (PLB-985 and CosPhoxFcγR, respectively) and in primary macrophages, we demonstrate that ARHGAP25 is a negative regulator of phagocytosis acting probably via modulation of the actin cytoskeleton.
authors.affiliation: Department of Physiology, Semmelweis University, Budapest, Hungary.
authors.forename: Roland
authors.initials: R
authors.lastname: Csépányi-Kömi
authors.forename: Gábor
authors.initials: G
authors.lastname: Sirokmány
authors.forename: Miklós
authors.initials: M
authors.lastname: Geiszt
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Ligeti
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008264:Macrophages / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C497035:ARHGAP25 protein, human; D000199:Actins; D020690:GTPase-Activating Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013481:Superoxides; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein