View the Current Issue

Article

  • The EMBO Journal (2002) 21, 1597 - 1606
  • doi:10.1093/emboj/21.7.1597

Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system

Kai Matuschewski1,2, Alvaro C. Nunes1,3, Victor Nussenzweig1 and Robert Ménard4

  1. Michael Heidelberger Division of Immunology, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
  2. Present address: Department of Parasitology, Heidelberg University School of Medicine, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany
  3. Present address: Universidade Federal de Minas Geiras, Department of Genetics, Belo Horizonte-MG, Brazil
  4. Laboratoire de Biologie et Génétique du Paludisme, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France

Correspondence to:

Robert Ménard, E-mail: rmenard@pasteur.fr

Received 29 November 2001; Accepted 21 January 2002; Revised 21 January 2002

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.

  • Keywords:

    • A-domain,
    • cell invasion,
    • Plasmodium,
    • thrombospondin type I repeat,
    • TRAP