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

Cell Host Microbe. 2016 Dec 14;20(6):731-743. doi: 10.1016/j.chom.2016.10.020.

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.

Keywords: actin dynamic; apicomplexa; glideosome; gliding motility; invasion and egress; lysine methyltransferase; microneme; phosphatidic acid; plasmodium; toxoplasma.

MeSH terms

  • Actin Cytoskeleton / physiology
  • Actins / physiology
  • Animals
  • Apicomplexa / cytology*
  • Apicomplexa / metabolism
  • Apicomplexa / physiology*
  • Cell Adhesion Molecules / physiology
  • Cell Movement
  • Exocytosis / physiology
  • Lipids*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Methyltransferases / metabolism
  • Microfilament Proteins / metabolism
  • Microfilament Proteins / physiology*
  • Models, Molecular
  • Molecular Motor Proteins / physiology*
  • Organelles
  • Phosphatidic Acids / metabolism
  • Plasmodium berghei / metabolism
  • Plasmodium berghei / physiology
  • Protein Conformation
  • Protozoan Infections / parasitology
  • Protozoan Proteins / metabolism
  • Protozoan Proteins / physiology*
  • Rabbits
  • Toxoplasma / cytology
  • Toxoplasma / metabolism
  • Toxoplasma / physiology
  • Toxoplasmosis / parasitology

Substances

  • Actins
  • Cell Adhesion Molecules
  • Lipids
  • MIC2 protein, Toxoplasma gondii
  • Membrane Proteins
  • Microfilament Proteins
  • Molecular Motor Proteins
  • Phosphatidic Acids
  • Protozoan Proteins
  • Methyltransferases