An Apicomplexan Actin-Binding Protein Serves as a Connector and Lipid Sensor to Coordinate Motility and Invasion

• Published in: Cell host & microbe Vol. 20; no. 6; pp. 731 - 743
• Main Authors: Jacot, Damien, Tosetti, Nicolò, Pires, Isa, Stock, Jessica, Graindorge, Arnault, Hung, Yu-Fu, Han, Huijong, Tewari, Rita, Kursula, Inari, Soldati-Favre, Dominique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.12.2016
• Subjects: Actin Cytoskeleton - physiology; actin dynamic; Actins - physiology; Animals; apicomplexa; Apicomplexa - cytology; Apicomplexa - metabolism; Apicomplexa - physiology; Cell Adhesion Molecules - physiology; Cell Movement; Exocytosis - physiology; glideosome; gliding motility; invasion and egress; Lipids; lysine methyltransferase; Membrane Proteins - metabolism; Membrane Proteins - physiology; Methyltransferases - metabolism; Microfilament Proteins - metabolism; Microfilament Proteins - physiology; microneme; Models, Molecular; Molecular Motor Proteins - physiology; Organelles; phosphatidic acid; Phosphatidic Acids - metabolism; plasmodium; Plasmodium berghei - metabolism; Plasmodium berghei - physiology; Protein Conformation; Protozoan Infections - parasitology; Protozoan Proteins - metabolism; Protozoan Proteins - physiology; Rabbits; toxoplasma; Toxoplasma - cytology; Toxoplasma - metabolism; Toxoplasma - physiology; Toxoplasmosis - parasitology; invasion and egress; lysine methyltransferase; gliding motility; apicomplexa; toxoplasma; plasmodium; phosphatidic acid; microneme; actin dynamic; glideosome
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2016.10.020

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. [Display omitted] •The Apicomplexa require a glideosome-associated connector (GAC) for motility and invasion•GAC is an actin-binding protein that stabilizes parasite F-actin•GAC binds to the adhesin MIC2 and phosphatidic acid to coordinate motility•An apical lysine methyltransferase is crucial for the apical positioning of GAC Host cell invasion by apicomplexan parasites involves gliding motility that is powered by rearward translocation of secreted transmembrane adhesins by the parasite actomyosin system. Jacot et al. identify a connector that bridges this actomyosin system to parasite adhesin-host receptor complexes, ensuring the propelling of these intracellular parasites into host cells.