title: The Plasmodium TRAP/MIC2 family member, TRAP-Like Protein (TLP), is involved in tissue traversal by sporozoites.
abstract: In the apicomplexan protozoans motility and cell invasion are mediated by the TRAP/MIC2 family of transmembrane proteins, members of which link extracellular adhesion to the intracellular actomyosin motor complex. Here we characterize a new member of the TRAP/MIC2 family, named TRAP-Like Protein (TLP), that is highly conserved within the Plasmodium genus. Similar to the Plasmodium sporozoite protein, TRAP, and the ookinete protein, CTRP, TLP possesses an extracellular domain architecture that is comprised of von Willebrand factor A (vWA) and thrombospondin type 1 (TSP1) domains, plus a short cytoplasmic domain. Comparison of the vWA domain of TLP genes from multiple Plasmodium falciparum isolates showed relative low sequence diversity, suggesting that the protein is not under selective pressures of the host immune system. Analysis of transcript levels by quantitative reverse transcription polymerase chain reaction (RT-PCR) showed that TLP is predominantly expressed in salivary gland sporozoites of P. falciparum and P. berghei. Targeted disruption of P. berghei TLP resulted in a decreased capacity for cell traversal by sporozoites, and reduced infectivity of sporozoites in vivo, whereas in vitro sporozoite motility and hepatocyte invasion were unaffected. These results indicate a role of TLP in cell traversal by sporozoites.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Cristina K
authors.initials: CK
authors.lastname: Moreira
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Templeton
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavazec
authors.forename: Rhian E
authors.initials: RE
authors.lastname: Hayward
authors.forename: Charlotte V
authors.initials: CV
authors.lastname: Hobbs
authors.forename: Hans
authors.initials: H
authors.lastname: Kroeze
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Waters
authors.forename: Photini
authors.initials: P
authors.lastname: Sinnis
authors.forename: Alida
authors.initials: A
authors.lastname: Coppi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002465:Cell Movement; D009033:Culicidae / Q000382:microbiology; D004912:Erythrocytes / Q000382:microbiology; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000166:cytology / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D034101:Sporozoites / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan