Ookinete-interacting proteins on the microvillar surface are partitioned into detergent resistant membranes of anopheles gambiae midguts

Lindsay A. Parish, David R. Colquhoun, Ceereena Ubaida Mohien, Alexey E. Lyashkov, David R. Graham, Rhoel R. Dinglasan

Research output: Contribution to journalArticlepeer-review

Abstract

Lipid raft microdomains, a component of detergent resistant membranes (DRMs), are routinely exploited by pathogens during host-cell entry. Multiple membrane-surface proteins mediate Plasmodium ookinete invasion of the Anopheles midgut, a critical step in the parasite life cycle that is successfully targeted by transmission-blocking vaccines (TBV). Given that lipid rafts are a common feature of host-pathogen interactions, we hypothesized that they promote the partitioning of midgut surface proteins and thus facilitate ookinete invasion. In support of this hypothesis, we found that five of the characterized Anopheles TBV candidates, including the leading Anopheles TBV candidate, AgAPN1, are present in Anopheles gambiae DRMs. Therefore, to extend the repertoire of putative midgut ligands that can be targeted by TBVs, we analyzed midgut DRMs by tandem mass spectrometry. We identified 1452 proteins including several markers of DRMs. Since glycosylphosphotidyl inositol (GPI)-anchored proteins partition to DRMs, we characterized the GPI subproteome of An. gambiae midgut brush-border microvilli and found that 96.9% of the proteins identified in the GPI-anchored fractions were also present in DRMs. Our study vastly expands the number of candidate malarial TBV targets for subsequent analysis by the broader community and provides an inferred role for midgut plasmalemma microdomains in ookinete cell invasion.

Original languageEnglish (US)
Pages (from-to)5150-5162
Number of pages13
JournalJournal of proteome research
Volume10
Issue number11
DOIs
StatePublished - Nov 4 2011

Keywords

  • Anopheles gambiae
  • Plasmodium
  • lipid rafts
  • malaria
  • midgut
  • ookinete
  • transmission blocking vaccine, detergent resistant membranes

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint Dive into the research topics of 'Ookinete-interacting proteins on the microvillar surface are partitioned into detergent resistant membranes of anopheles gambiae midguts'. Together they form a unique fingerprint.

Cite this