Abstract
Schistosomiasis caused by schsitosomes is a serious global public health concern. The tegument that surrounds the worm is critical to the schistosomes survival. The tegument apical membrane undergoes a continuous process of rupture and repair owing to membranous vacuoles fusing with the plasma membrane. Vesicle-associated membrane protein 2 (VAMP2), a member of soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNAREs) is required for membrane fusion. Here, we used RNA interference (RNAi) to knock down the expression of VAMP2 of Schistosoma japonicum (SjVAMP2), and both real-time PCR and western blot analysis confirmed the suppression of this molecule, as well as the suppression of the transcript levels of schistosome glucose transporters (SGTP1 and SGTP4), and insulin receptors (SjIR1 and SjIR2). SjVAMP2-suppressed worms exhibited a lower viability, and phenotypic alterations were also observed in the tegument. Moreover, the glucose consumption of SjVAMP2-suppressed worms decreased significantly in 4 and 6 days, respectively, as well as a significant reduction in egg production. We also observed a significant reduction in worm burden and hepatic eggs burden in two independent RNAi experiment in vivo, and minor pathological changes in mice treated with SjVAMP2 specific small interfering (si)RNA. These findings reveal that SjVAMP2 may play important roles in the maintenance of tegument, glucose uptake, worm development and egg production in schistosomes.
Highlights
The entire worm is surrounded by a continuous cytoplasmic membrane, or syncytium, known as the tegument which is the direct interface between the parasite and its host[6]
The core proteins implicated in this process are soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) localized in opposing membranes, including synaptobrevin/Vesicle-associated membrane protein 2 (VAMP2) on the vesicle membrane (v-SNARE), syntaxin and 25-kDa synaptosome-associated protein (SNAP-25) families on the target membrane (t-SNARE)
Glucose is uptaken via two glucose transporter proteins (GTPs): SGTP1 and SGTP432–34, and it has been reported that the suppression of genes SGTP1 or SGTP4 in Schistosoma mansoni (S. mansoni) using RNA interference (RNAi) impairs the ability to intake glucose[35]
Summary
The entire worm is surrounded by a continuous cytoplasmic membrane, or syncytium, known as the tegument which is the direct interface between the parasite and its host[6]. In non-neuronal tissues, VAMP2 is involved in the regulation of exocytosis including insulin secretion in pancreatic β-cells[24], fusion of lytic granules in cytotoxic T-lymphocytes[25], insulin-dependent translocation of GLUT4-containing vesicles in adipocytes[26, 27] and muscle regeneration in quiescent satellite cells[28, 29]. GLUT4-containing vesicles colocalized with VAMP2 fuse with the plasma membrane of insulin-sensitive cells to stimulate glucose uptake. Our research group cloned this gene and showed that SjVAMP2 was primarily expressed in the tegument of schistosomes; in addition, its transcripts were highly expressed in 42-day female worms[43]. Despite these promising results, the biological functions of SjVAMP2 have not been fully elucidated in S. japonicum. We employed the RNA interference (RNAi) technique[44] to explore the functional role of SjVAMP2 in worm growth, development, and female fecundity
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