Amino acid transport in schistosomes: Characterization of the permeaseheavy chain SPRM1hc

J Biol Chem. 2007 Jul 27;282(30):21767-75. doi: 10.1074/jbc.M703512200. Epub 2007 Jun 1.

Abstract

Schistosomes are human parasitic flatworms that constitute an important public health problem globally. Adult parasites live in the bloodstream where they import nutrients such as amino acids across their body surface (the tegument). One amino acid transporter, Schistosome Permease 1 light chain, SPRM1lc, a member of the glycoprotein-associated family of transporters (gpaAT), has been characterized in schistosomes. Only a single member of the SLC3 family of glycoproteins that associate with gpaATs is found following extensive searching of the genomes of Schistosoma mansoni and S. japonicum. In this report, we characterize this schistosome permease heavy chain (SPRM1hc) gene and protein. The 72-kDa gene product is predicted to possess a single transmembrane domain, a (betaalpha)(8) (TIM barrel) conformation and a catalytic triad. Xenopus oocytes functionally expressing SPRM1hc with SPRM1lc import phenylalanine, arginine, lysine, alanine, glutamine, histidine, tryptophan, and leucine. Biochemical characterization demonstrates that in Xenopus extracts and in schistosome extracts SPRM1hc is associated into a high molecular weight complex with SPRM1lc that is disrupted by reducing agents. Quantitative real-time PCR and Western analysis demonstrate that SPRM1hc is expressed in each schistosome life stage examined (eggs, cercariae, schistosomula, adult males and females). SPRM1hc is widely distributed throughout adult male and female worms as determined by immunolocalization. Consistent with the hypothesis that SPRM1hc functions to facilitate nutrient uptake from host blood, immunogold electron microscopy confirms that the protein is distributed on the host-interactive tegumental membranes. We propose that surface-exposed, host-interactive, nutrient-transporting proteins like the SPRM1 heterodimer are promising vaccine candidates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Biological Transport
  • Biomphalaria / parasitology
  • DNA, Helminth / genetics
  • Expressed Sequence Tags
  • Fusion Regulatory Protein 1, Light Chains / genetics*
  • Fusion Regulatory Protein 1, Light Chains / metabolism*
  • Helminth Proteins / genetics*
  • Helminth Proteins / metabolism*
  • Oocytes / physiology
  • Polymerase Chain Reaction
  • Schistosoma japonicum / genetics
  • Schistosoma japonicum / metabolism
  • Schistosoma mansoni / genetics
  • Schistosoma mansoni / metabolism*
  • Transfection
  • Xenopus

Substances

  • Amino Acids
  • DNA, Helminth
  • Fusion Regulatory Protein 1, Light Chains
  • Helminth Proteins
  • SPRM1lc transport protein, Schistosoma mansoni