569 SPRM1lc, a heterodimeric amino acid permease light chain of the human parasitic platyhelminth, Schistosoma mansoni P.J.SKELLY *, R.PFEIFFER , F. VERREY  and C.B.SHOEMAKER   Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115  Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland (Received 25 May 1999; revised 12 July 1999; accepted 12 July 1999)  The Schistosoma mansoni protein, SPRM1lc, is a light chain member of a new family of heterodimeric amino acid permeases. These proteins require covalent association with a type II glycoprotein (like h4F2hc) for functional surface localization when expressed in Xenopus oocytes. We previously reported that, when co-expressed with h4F2hc, the transport properties of SPRM1lc resemble system y and y + while its human homologue, E16, functions as an L-type permease. Here we extend the functional characterization of SPRM1lc in oocytes and show by competitor studies that its amino acid transport capacity is similar to that of whole adult schistosomes. We demonstrate by Northern and Western analysis that SPRM1lc is expressed within both larval and adult schistosomes. In all stages, SPRM1lc is associated into a high molecular weight complex that can be disrupted by reducing agents, consistent with the hypothesis that a significant fraction of the endogenous SPRM1lc is linked by a disulphide bond to an uncharacterized schistosome amino acid transporter heavy chain. Immunofluorescence localization detects SPRM1lc in miracidia, daughter sporocysts and adult worms. Confocal microscopy demonstrates that SPRM1lc is found in the apical membrane of the syncytial, double-lipid bilayer tegument which surrounds adult worms. Aqueous biotinylation studies on living worms show that SPRM1lc is exposed on the host-interactive surface of this tegumental membrane. Host exposed, functionally important surface proteins such as SPRM1lc could form the basis of an effective schistosomiasis vaccine. These studies are the first to describe a helminth amino acid transporter, and the first to characterize an invertebrate heterodimeric amino acid transporter. Key words : schistosome, amino acid permeasetransporter, nutrient uptake, tegument.  Schistosomes are parasitic platyhelminths that cause the debilitating disease schistosomiasis affecting several hundred million people globally. The para- sites exhibit a complex life-history in which they undertake asexual multiplication in an intermediate freshwater snail host and attain sexual maturity in their final vertebrate hosts. Adult schistosomes live in the vertebrate bloodstream where they import nutrients across the syncytial, double-lipid bilayer membrane, called the tegument, which surrounds the entire worm. This suggests that nutrient trans- porter proteins (or permeases) must be located in the outer, apical membrane of the tegument and must be exposed to the nutrients in the serum. Such host- exposed membrane proteins might make excellent targets for immunological or chemotherapeutic in- tervention. Several glucose transporters have been charac- * Corresponding author : Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Tel : 617 432 1339. Fax: 617 738 4914. E-mail: psk hsph.harvard.edu terized in schistosomes (Skelly et al. 1994) and one of these, SGTP4, is detected only at the host interactive apical membrane of the tegument in mammalian stage Schistosoma mansoni (Skelly & Shoemaker, 1996). SGTP4 expression is rapidly induced upon transformation of larval cercariae into schistosomula at the time of infection. The protein is then deposited onto the surface of the worms as they shed their cercarial glycocalyx and synthesize the new tegu- ment. Presumably this transporter is needed to replenish hexose reserves utilized during the move- ment of the cercariae from the snail to its final host, and to accommodate the shift from oxidative glucose metabolism to largely anaerobic lactate fermentation. SGTP4 remains present in the apical tegumental membrane through adult development. A second glucose transporter, SGTP1, is localized within the basal membrane of the tegument and internal membranes, and may distribute the glucose from the tegument to the rest of the worm (Skelly, Tielens & Shoemaker, 1998). Little is known as to how schistosomes facilitate the uptake of other critical nutrients during their complicated life-cycle. Recently we reported that cDNA encoding an S. mansoni amino acid permease, SPRM1lc, functioned Parasitology (1999), 119, 569–576. Printed in the United Kingdom  1999 Cambridge University Press