Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany; Université de Strasbourg, CNRS UPR9022, INSERM U963, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France
Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany; Department of Molecular Virology, Heidelberg University Medical School, Heidelberg, Germany
Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany; Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, München, Germany
Chafen Lu
Program in Cellular and Molecular Medicine, Children's Hospital Boston, and Departments of Biological Chemistry and Molecular Pharmacology and of Medicine, Harvard Medical School, Boston, United States
Program in Cellular and Molecular Medicine, Children's Hospital Boston, and Departments of Biological Chemistry and Molecular Pharmacology and of Medicine, Harvard Medical School, Boston, United States
Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin αβ heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aX I domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla.