Thrombospondin-related adhesive protein (TRAP) of Plasmodium falciparum: expression during sporozoite ontogeny and binding to human hepatocytes.
Plasmodium sporozoites collected from oocysts, haemocoel and salivary glands of the mosquito show profound differences in their biological properties such as motility, ability to induce protective immune response and infectivity for vertebrate host cells. Sporozoites from salivary glands are much more infectious than those from oocysts and haemocoel. Differential expression of proteins, such as the circumsporozoite (CS) protein and the thrombospondin-related adhesive protein (TRAP), implicated in sporozoite recognition and entry into hepatocytes may account for the development of infectivity during ontogeny. We have carried out a series of experiments to: (i) analyse the expression and localization of TRAP in P.falciparum sporozoites during development in the mosquito; and (ii) elucidate the biochemical and adhesive properties of recombinant TRAP. Our data indicate that TRAP is not expressed in oocysts, whereas variable amounts of CS protein are found in this parasite developmental stage. Hemocoel sporozoites display the distinct phenotypes TRAP- CS protein+ and TRAP+ CS protein+ at a frequency of 98.5 and 1.5% respectively. Salivary gland sporozoites are all TRAP+ CS protein+. We also provide experimental evidence showing that recombinant TRAP binds to the basolateral cell membrane of hepatocytes in the Disse's space and that sulfated glycoconjugates function as TRAP ligands on human hepatocytes.
Robson
K J
KJ
MRC Molecular Haematology Unit, John Radcliffe Hospital, Headington, Oxford, UK.
Frevert
U
U
Reckmann
I
I
Cowan
G
G
Beier
J
J
Scragg
I G
IG
Takehara
K
K
Bishop
D H
DH
Pradel
G
G
Sinden
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012469:Salivary Glands / Q000469:parasitology; D013464:Sulfuric Acids; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006001:Glycoconjugates; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D013464:Sulfuric Acids; C041595:circumsporozoite protein, Protozoan; C069428:thrombospondin-related adhesive protein, protozoan; C033158:sulfuric acid