Anopheles Midgut FREP1 Mediates Plasmodium Invasion.

Abstract

Malaria transmission depends on sexual stage Plasmodium parasites successfully invading Anopheline mosquito midguts following a blood meal. However, the molecular mechanisms of Plasmodium invasion of mosquito midguts have not been fully elucidated. Previously, we showed that genetic polymorphisms in the fibrinogen-related protein 1 (FREP1) gene are significantly associated with Plasmodium falciparum infection in Anopheles gambiae, and FREP1 is important for Plasmodium berghei infection of mosquitoes. Here we identify that the FREP1 protein is secreted from the mosquito midgut epithelium and integrated as tetramers into the peritrophic matrix, a chitinous matrix formed inside the midgut lumen after a blood meal feeding. Moreover, we show that the FREP1 can directly bind Plasmodia sexual stage gametocytes and ookinetes. Notably, ablating FREP1 expression or targeting FREP1 with antibodies significantly decreases P. falciparum infection in mosquito midguts. Our data support that the mosquito-expressed FREP1 mediates mosquito midgut invasion by multiple species of Plasmodium parasites via anchoring ookinetes to the peritrophic matrix and enabling parasites to penetrate the peritrophic matrix and the epithelium. Thus, targeting FREP1 can limit malaria transmission.

• Authors: Genwei Zhang, Guodong Niu, Caio M Franca, Yuemei Dong, Xiaohong Wang, Noah S Butler, George Dimopoulos, Jun Li
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 27 Pg. 16490-501 (Jul 03 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 25991725 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Insect Proteins
• Fibrinogen

Topics

• Animals
• Anopheles (genetics, growth & development, metabolism, parasitology)
• Digestive System (metabolism, parasitology)
• Female
• Fibrinogen (genetics, metabolism)
• Host-Parasite Interactions
• Insect Proteins (genetics, metabolism)
• Insect Vectors (genetics, growth & development, metabolism, parasitology)
• Male
• Plasmodium falciparum (physiology)