Cloning, characterization, and functional expression of cDNAs encoding glucose transporter proteins from the human parasite Schistosoma mansoni

• Published in: The Journal of biological chemistry Vol. 269; no. 6; pp. 4247 - 4253
• Main Authors: SKELLY, P. J, JUNG WOO KIM, CUNNINGHAM, J, SHOEMAKER, C. B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 11.02.1994
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Binding and carrier proteins; Biological and medical sciences; Biological Transport; Cloning, Molecular; Deoxyglucose - metabolism; DNA Primers - chemistry; DNA, Complementary - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Genes, Helminth; Male; Molecular Sequence Data; Monosaccharide Transport Proteins - chemistry; Monosaccharide Transport Proteins - genetics; Mutagenesis, Site-Directed; Proteins; Recombinant Proteins - metabolism; Restriction Mapping; RNA, Messenger - genetics; Schistosoma mansoni; Schistosoma mansoni - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Structure-Activity Relationship; Schistosoma mansoni; Regulation(control); Substrate specificity; Helmintha; Plathelmintha; Glucose; Invertebrata; Molecular cloning; Carrier protein; Trematoda; Biological activity; Aminoacid sequence
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)41770-4

The blood-dwelling adult form of the parasitic worm, Schistosoma mansoni, consumes prodigious quantities of host glucose following its transport across the tegument. Immunologic or pharmacologic targeting of the relevant transporter proteins might form the basis of a schistosome control strategy. Here we report the isolation and characterization of three different full-length cDNAs whose predicted protein sequences show a high degree of sequence and structural similarity to the facilitated diffusion transporter proteins of other animals, plants, and bacteria. Functional expression of two cDNAs has been achieved by injection of Xenopus oocytes with in vitro derived sense strand RNA. Injected oocytes have a significantly increased ability to take up radiolabeled glucose analogues over controls. S. mansoni glucose transporters expressed in oocytes exhibit stereospecificity for D-glucose, have relaxed specificity for different hexoses, exhibit sodium independence, and are markedly inhibited by phloretin and cytochalasin B. These two transporters, expressed in oocytes, have a Km for 3-O-methylglucose of 1.3 and 2 mM. A third glucose transporter homologue cDNA appears to derive from a recent pseudogene. Both of the functional S. mansoni glucose transporter genes are expressed in larval and adult male and female schistosomes.