Abstract
Clonorchis sinensis is a liver fluke that can dwell in the bile ducts of mammals. Bile acid transporters function to maintain the homeostasis of bile acids in C. sinensis, as they induce physiological changes or have harmful effects on C. sinensis survival. The organic solute transporter (OST) transports mainly bile acid and belongs to the SLC51 subfamily of solute carrier transporters. OST plays a critical role in the recirculation of bile acids in higher animals. In this study, we cloned full-length cDNA of the 480-amino acid OST from C. sinensis (CsOST). Genomic analysis revealed 11 exons and nine introns. The CsOST protein had a ‘Solute_trans_a’ domain with 67% homology to Schistosoma japonicum OST. For further analysis, the CsOST protein sequence was split into the ordered domain (CsOST-N) at the N-terminus and disordered domain (CsOST-C) at the C-terminus. The tertiary structure of each domain was built using a threading-based method and determined by manual comparison. In a phylogenetic tree, the CsOST-N domain belonged to the OSTα and CsOST-C to the OSTβ clade. These two domains were more highly conserved with the OST α- and β-subunits at the structure level than at sequence level. These findings suggested that CsOST comprised the OST α- and β-subunits. CsOST was localized in the oral and ventral suckers and in the mesenchymal tissues abundant around the intestine, vitelline glands, uterus, and testes. This study provides fundamental data for the further understanding of homologues in other flukes.
Highlights
Clonorchis sinensis is a liver fluke that parasitizes the bile ducts of mammals [1]
When sequences of the Expressed sequence tag (EST) clone and rapid amplification of cDNA ends (RACE) product were assembled, the full-length cDNA of C. sinensis organic solute transporter (CsOST) was elongated to 1725 bp, encoding a putative polypeptide of 480 amino acids and containing 50-untranslated region
The CsOST-N and CsOST-C were conserved with canonical organic solute transporter (OST) α- and β-subunits, and showed positional conservation rather than overall sequence conservation
Summary
Clonorchis sinensis is a liver fluke that parasitizes the bile ducts of mammals [1]. C. sinensis causes numerous pathophysiological primary and secondary changes, such as inflammation, hyperplasia of epithelial cells, metaplasia in the mucosa, and periductal fibrosis [6]. Feeding of LCA intrinsically causes bile duct injury in mice [9]. In addition to abnormal bile composition, disturbances of either normal flow or transport of bile across membranes may result in the formation of toxic bile. Bile toxicity can be prevented by its export via bile transporters These transporters include multidrug resistance proteins 3 (MRP3) [11], MRP4 [12], bile salts export pump (BSEP) [13], and organic solute transporter (OST) [14]. Bile flow and circulation via the bile efflux transporters is crucial in reducing bile toxicity and limiting its interaction with cell membranes
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