Da'dara A, Krautz-Peterson G, Faghiri Z, Skelly P J
Molecular Helminthology Laboratory, Department of Biomedical Sciences, Division of Infectious Diseases, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA.
J Helminthol. 2012 Jun;86(2):141-7. doi: 10.1017/S0022149X12000120. Epub 2012 Feb 27.
Intravascular schistosome parasites are covered by an unusual double lipid bilayer. Nutrients, such as glucose and amino acids, as well as other metabolites, are known to be transported across this surface via specific transporter proteins. For instance, the glucose transporter protein SGTP4 is found in the host-interactive tegumental membranes. A second glucose transporter, SGTP1, localizes to the tegumental basal membrane (and internal tissues). Following expression in Xenopus oocytes, SGTP1 and SGTP4 both function as facilitated-diffusion sugar transporters. Suppressing the expression of SGTP1 and SGTP4 in juvenile schistosomes using RNA interference (RNAi) impairs the parasite's ability to import glucose and severely decreases worm viability. Amino acids can also be imported into schistosomes across their surface and an amino acid transporter (SPRM1lc) has been localized in the parasite surface membranes (as well as internally). In Xenopus oocytes, SPRM1lc can import the basic amino acids arginine, lysine and histidine as well as leucine, phenylalanine, methionine and glutamine. To function, this protein requires the assistance of a heavy-chain partner (SPRM1hc) which acts as a chaperone. Water is transported across the tegument of schistosomes via the aquaporin protein SmAQP. Suppressing SmAQP gene expression makes the parasites less able to osmoregulate and decreases their viability. In addition, SmAQP-suppressed adult parasites have been shown to be impaired in their ability to excrete lactate. Analysis of tegumental transporter proteins, as described in this report, is designed to generate a comprehensive understanding of the role of such proteins in promoting parasite survival by controlling the movement of metabolites into and out of the worms.
血管内的血吸虫寄生虫被一层不同寻常的双脂质双层所覆盖。已知葡萄糖和氨基酸等营养物质以及其他代谢产物是通过特定的转运蛋白跨这一表面进行运输的。例如,葡萄糖转运蛋白SGTP4存在于与宿主相互作用的皮层膜中。另一种葡萄糖转运蛋白SGTP1定位于皮层基底膜(以及内部组织)。在非洲爪蟾卵母细胞中表达后,SGTP1和SGTP4均作为易化扩散型糖转运蛋白发挥作用。利用RNA干扰(RNAi)抑制幼年血吸虫中SGTP1和SGTP4的表达会损害寄生虫摄取葡萄糖的能力,并严重降低虫体活力。氨基酸也可以通过其表面进入血吸虫,一种氨基酸转运蛋白(SPRM1lc)已定位在寄生虫表面膜(以及内部)。在非洲爪蟾卵母细胞中,SPRM1lc可以转运碱性氨基酸精氨酸、赖氨酸和组氨酸以及亮氨酸、苯丙氨酸、蛋氨酸和谷氨酰胺。为发挥功能,该蛋白需要一个重链伴侣(SPRM1hc)的协助,后者起分子伴侣的作用。水通过水通道蛋白SmAQP跨血吸虫的皮层进行运输。抑制SmAQP基因表达会使寄生虫的渗透调节能力下降,并降低其活力。此外,已证明抑制SmAQP的成年寄生虫排泄乳酸的能力受损。如本报告所述,对皮层转运蛋白的分析旨在全面了解此类蛋白通过控制代谢产物进出虫体的运动在促进寄生虫存活中的作用。