Role of Plasmodium falciparum thrombospondin-related anonymous protein in host-cell interactions.

Malaria Journal
Reetesh Raj AkhouriAmit Sharma

Abstract

Thrombospondin-related anonymous protein (TRAP) is essential for sporozoite motility and for liver cell invasion. TRAP is a type 1 membrane protein that possesses multiple adhesive domains in its extracellular region. Plasmodium falciparum TRAP (PfTRAP) and its subdomains were expressed in a mammalian expression system, and eleven different mutants generated to study interaction of PfTRAP with liver cells. Binding studies between HepG2 cell extracts and PfTRAP were performed using co-immunoprecipitation protocols. Five different amino acid residues of PfTRAP that are involved in liver cell binding have been identified. These PfTRAP mutants bound to heparin like the wild type PfTRAP thereby suggesting a non-heparin mediated binding of PfTRAP to liver cells. Three Src family proteins -Lyn, Lck and CrkL which interact with PfTRAP are also identified. Liver cell extracts and immunoprecipitated Src family kinases phosphorylated PfTRAP at multiple sites. An analysis of multiple TRAP sequences revealed Src homology 3 domain (SH3) binding motifs. Binding of PfTRAP to SH3-domain containing proteins like Src-family kinases and their ability to phosphorylate PfTRAP suggests a novel role for PfTRAP in cell signaling during sporozoite invas...Continue Reading

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Citations

Aug 12, 2010·Malaria Journal·Pantelis TopalisChristos Louis
Nov 21, 2012·PLoS Pathogens·S Josefin BartholdsonGavin J Wright
Oct 30, 2015·Expert Review of Vaccines·Sarah Sebastian, Sarah C Gilbert
Dec 6, 2014·Trends in Biochemical Sciences·Allegra ViaAndreas Zanzoni
Jan 28, 2017·Immunotherapy·Manuel E PatarroyoJorge Aza-Conde
Sep 28, 2020·Parasite Immunology·Kelvin Mokaya AbugaJulius Clemence R Hafalla
Feb 17, 2021·Trends in Parasitology·Silvia A ArredondoStefan H I Kappe
Jun 5, 2020·Central Nervous System Agents in Medicinal Chemistry·Akeem A AyankunleOluwaseyi A Adeyeba

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Methods Mentioned

BETA
PCR
transfection
transfections
FACS
pull down
gel filtration
ELISA
gel-filtration
flow cytometry
immunoprecipitations

Software Mentioned

FACS

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