title: Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity.
abstract: The circumsporozoite protein of Plasmodium falciparum contains two conserved motifs (regions I and II) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. These data shed new light on the role of the CS protein in sporozoite motility and infectivity.
authors.affiliation: Imperial College of Science, Technology and Medicine, Imperial College Road, London SW7 2AZ, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
authors.forename: Roberta
authors.initials: R
authors.lastname: Spaccapelo
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000852:Anopheles / Q000378:metabolism; D015139:Blotting, Southern; D004912:Erythrocytes / Q000469:parasitology; D007422:Intestines / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009068:Movement; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D012469:Salivary Glands / Q000469:parasitology; D017386:Sequence Homology, Amino Acid; D034101:Sporozoites / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan