Malaria parasite invasion of the mosquito salivary gland requires interaction between the Plasmodium TRAP and the Anopheles saglin proteins.
SM1 is a twelve-amino-acid peptide that binds tightly to the Anopheles salivary gland and inhibits its invasion by Plasmodium sporozoites. By use of UV-crosslinking experiments between the peptide and its salivary gland target protein, we have identified the Anopheles salivary protein, saglin, as the receptor for SM1. Furthermore, by use of an anti-SM1 antibody, we have determined that the peptide is a mimotope of the Plasmodium sporozoite Thrombospondin Related Anonymous Protein (TRAP). TRAP binds to saglin with high specificity. Point mutations in TRAP's binding domain A abrogate binding, and binding is competed for by the SM1 peptide. Importantly, in vivo down-regulation of saglin expression results in strong inhibition of salivary gland invasion. Together, the results suggest that saglin/TRAP interaction is crucial for salivary gland invasion by Plasmodium sporozoites.
Ghosh
Anil K
AK
Department of Molecular Microbiology and Immunology and Malaria Research Institute, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America.
Devenport
Martin
M
Jethwaney
Deepa
D
Kalume
Dario E
DE
Pandey
Akhilesh
A
Anderson
Vernon E
VE
Sultan
Ali A
AA
Kumar
Nirbhay
N
Jacobs-Lorena
Marcelo
M
D000818:Animals; D000852:Anopheles / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000502:physiology; D019476:Insect Proteins / Q000378:metabolism*; D008288:Malaria / Q000635:transmission; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000469:parasitology; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D034101:Sporozoites / Q000502:physiology
D019476:Insect Proteins; D009842:Oligopeptides; D015800:Protozoan Proteins; C535223:SM1 peptide; D012471:Salivary Proteins and Peptides; C535222:saglin protein, Anopheles gambiae; C069428:thrombospondin-related adhesive protein, protozoan