title: An Apicomplexan Actin-Binding Protein Serves as a Connector and Lipid Sensor to Coordinate Motility and Invasion.
abstract: Apicomplexa exhibit a unique form of substrate-dependent gliding motility central for host cell invasion and parasite dissemination. Gliding is powered by rearward translocation of apically secreted transmembrane adhesins via their interaction with the parasite actomyosin system. We report a conserved armadillo and pleckstrin homology (PH) domain-containing protein, termed glideosome-associated connector (GAC), that mediates apicomplexan gliding motility, invasion, and egress by connecting the micronemal adhesins with the actomyosin system. TgGAC binds to and stabilizes filamentous actin and specifically associates with the transmembrane adhesin TgMIC2. GAC localizes to the apical pole in invasive stages of Toxoplasma gondii and Plasmodium berghei, and apical positioning of TgGAC depends on an apical lysine methyltransferase, TgAKMT. GAC PH domain also binds to phosphatidic acid, a lipid mediator associated with microneme exocytosis. Collectively, these findings indicate a central role for GAC in spatially and temporally coordinating gliding motility and invasion.
authors.affiliation: Department of Microbiology & Molecular Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
authors.forename: Damien
authors.initials: D
authors.lastname: Jacot
authors.affiliation: Department of Microbiology & Molecular Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Tosetti
authors.affiliation: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220 Oulu, Finland.
authors.forename: Isa
authors.initials: I
authors.lastname: Pires
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Stock
authors.affiliation: Department of Microbiology & Molecular Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
authors.forename: Arnault
authors.initials: A
authors.lastname: Graindorge
authors.affiliation: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220 Oulu, Finland.
authors.forename: Yu-Fu
authors.initials: YF
authors.lastname: Hung
authors.affiliation: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220 Oulu, Finland.
authors.forename: Huijong
authors.initials: H
authors.lastname: Han
authors.affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham NG2 7UH, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.affiliation: Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7, 90220 Oulu, Finland; Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. Electronic address: inari.kursula@uib.no.
authors.forename: Inari
authors.initials: I
authors.lastname: Kursula
authors.affiliation: Department of Microbiology & Molecular Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva, Switzerland. Electronic address: dominique.soldati-favre@unige.ch.
authors.forename: Dominique
authors.initials: D
authors.lastname: Soldati-Favre
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000502:physiology; D000818:Animals; D016782:Apicomplexa / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D002465:Cell Movement; D005089:Exocytosis / Q000502:physiology; D008055:Lipids; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008780:Methyltransferases / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000502:physiology*; D015388:Organelles; D010712:Phosphatidic Acids / Q000378:metabolism; D010962:Plasmodium berghei / Q000378:metabolism / Q000502:physiology; D011487:Protein Conformation; D011528:Protozoan Infections / Q000469:parasitology; D015800:Protozoan Proteins / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D014122:Toxoplasma / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D014123:Toxoplasmosis / Q000469:parasitology
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008055:Lipids; C408878:MIC2 protein, Toxoplasma gondii; D008565:Membrane Proteins; D008840:Microfilament Proteins; D020409:Molecular Motor Proteins; D010712:Phosphatidic Acids; D015800:Protozoan Proteins; D008780:Methyltransferases
keywords: actin dynamic; apicomplexa; glideosome; gliding motility; invasion and egress; lysine methyltransferase; microneme; phosphatidic acid; plasmodium; toxoplasma