Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system.
Plasmodium sporozoites, the transmission form of the malaria parasite, successively invade salivary glands in the mosquito vector and the liver in the mammalian host. Sporozoite capacity to invade host cells is mechanistically related to their ability to glide on solid substrates, both activities depending on the transmembrane protein TRAP. Here, we show that loss-of- function mutations in two adhesive modules of the TRAP ectodomain, an integrin-like A-domain and a thrombospondin type I repeat, specifically decrease sporozoite invasion of host cells but do not affect sporozoite gliding and adhesion to cells. Irrespective of the target cell, i.e. in mosquitoes, rodents and cultured human or hamster cells, sporozoites bearing mutations in one module are less invasive, while those bearing mutations in both modules are non-invasive. In Chinese hamster ovary cells, the TRAP modules interact with distinct cell receptors during sporozoite invasion, and thus act as independently active pass keys. As these modules are also present in other members of the TRAP family of proteins in Apicomplexa, they may account for the capacity of these parasites to enter many cell types of phylogenetically distant origins.
Matuschewski
Kai
K
Michael Heidelberger Division of Immunology, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Nunes
Alvaro C
AC
Nussenzweig
Victor
V
Ménard
Robert
R
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D001665:Binding Sites; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D007313:Insecta; D008099:Liver / Q000469:parasitology; D008322:Mammals; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010962:Plasmodium berghei / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000469:parasitology
D015815:Cell Adhesion Molecules; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan