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Malaria Parasite Invasion of the Mosquito Salivary Gland Requires Interaction between the Plasmodium TRAP and the Anopheles Saglin Proteins

2009; Public Library of Science; Volume: 5; Issue: 1 Linguagem: Inglês

10.1371/journal.ppat.1000265

1553-7374

Anil K. Ghosh, Martin Devenport, Deepa Jethwaney, Dário Eluan Kalume, Akhilesh Pandey, Vernon Anderson, Ali A. Sultan, Nirbhay Kumar, Marcelo Jacobs-­Lorena,

Insect Resistance and Genetics

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.