Defective sorting of the thrombospondin-related anonymous protein (TRAP) inhibits Plasmodium infectivity.
Thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that plays an essential role in gliding motility and cell invasion by Plasmodium sporozoites. It is stored in micronemes-secretory organelles located primarily in the apical end of the parasites and is also found on the parasite surface. The mechanisms that target TRAP and other sporozoite proteins to micronemes and subsequently to the parasite surface are not known. Here we report that the micronemal and surface localization of TRAP requires a tyrosine-based motif located in its cytoplasmic tail. This motif is analogous to the YXXphi motif (Y: tyrosine, X: any amino acid; phi: hydrophobic amino acid) that targets eukaryotic proteins to certain sub-cellular compartments and to the plasma membrane. Abrogating the Y motif substantially reduces micronemal and cell surface localization of TRAP. The infectivity of mutant parasites is substantially inhibited. However, there is no significant difference in the amounts of TRAP secreted into the culture medium by wild type and mutant parasites, suggesting that TRAP destined for secretion bypasses micronemal localization.
Bhanot
Purnima
P
Michael Heidelberger Division of Immunology, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Frevert
Ute
U
Nussenzweig
Victor
V
Persson
Cathrine
C
D000595:Amino Acid Sequence; D000818:Animals; D019084:Fluorescent Antibody Technique, Indirect; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D010961:Plasmodium / Q000472:pathogenicity* / Q000502:physiology / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019699:Thrombospondins / Q000502:physiology*; D014122:Toxoplasma / Q000235:genetics
D015800:Protozoan Proteins; D011994:Recombinant Proteins; D019699:Thrombospondins; C069428:thrombospondin-related adhesive protein, protozoan