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

PLoS Pathogens

Vernon E. Anderson¹  Deepa Jethwaney²  Ali A. Sultan²  Marcelo Jacobs-Lorena³  Nirbhay Kumar³  Anil K. Ghosh³  Martin Devenport³  Akhilesh Pandey⁴  Dario E. Kalume⁴ 

[1] Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, United States of America;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America;Department of Molecular Microbiology and Immunology and Malaria Research Institute, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America;McKusick-Nathans Institute of Genetic Medicine and Departments of Biological Chemistry, Pathology, and Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America

关键词: Salivary gl;    s;    Sporozoites;    Plasmodium;    Mosquitoes;    Recombinant proteins;    Enzyme-linked immunoassays;    Double str;    ed RNA;    Carbohydrates;   

DOI  :  10.1371/journal.ppat.1000265

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY