Journal article
Anopheles Midgut FREP1 Mediates Plasmodium Invasion
The Journal of biological chemistry, Vol.290(27), pp.16490-16501
07/03/2015
DOI: 10.1074/jbc.m114.623165
PMCID: PMC4505404
PMID: 25991725
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.
Details
- Title: Subtitle
- Anopheles Midgut FREP1 Mediates Plasmodium Invasion
- Creators
- Genwei Zhang - From the Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019Guodong Niu - From the Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019Caio M Franca - From the Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019Yuemei Dong - the W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, andXiaohong Wang - University of OklahomaNoah S Butler - the Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104George Dimopoulos - the W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, andJun Li - From the Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, junli@ou.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.290(27), pp.16490-16501
- DOI
- 10.1074/jbc.m114.623165
- PMID
- 25991725
- PMCID
- PMC4505404
- NLM abbreviation
- J Biol Chem
- ISSN
- 1083-351X
- eISSN
- 1083-351X
- Publisher
- United States
- Grant note
- R21 AI115178 / NIAID NIH HHS GM103447 / NIGMS NIH HHS P20 GM103447 / NIGMS NIH HHS 1R21AI115178-01A1 / NIAID NIH HHS
- Language
- English
- Date published
- 07/03/2015
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001140302771
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