Proteomic Profiling of an Exosome-Enriched Extracellular Vesicle Fraction and Structural Characterization of SMPDL3A in the Carcinogenic Liver Fluke Clonorchis sinensis

TL;DR

This study explores exosomes from the liver fluke Clonorchis sinensis and identifies a protein, SMPDL3A, that may play a role in lipid metabolism and immune interactions during infection.

Contribution

The study provides structural and functional insights into Cs_SMPDL3A, a sphingomyelin phosphodiesterase in Clonorchis sinensis, suggesting its role in host–parasite lipid interactions.

Findings

Cs_SMPDL3A shares structural and catalytic features with mammalian sphingomyelin phosphodiesterases.

Cs_SMPDL3A may facilitate sphingomyelin metabolism on lipid bilayers via a transmembrane segment.

The protein could influence host immune responses or lipid availability during clonorchiasis.

Abstract

Exosomes are important mediators of host–parasite communication and contain diverse molecules that may support the survival of Clonorchis sinensis in the biliary tract. To explore their biochemical properties, exosomes isolated from excretory–secretory products of Korean C. sinensis isolates were characterized through integrated morphological, proteomic, and gene ontology analyses. The vesicles exhibited typical exosomal size ranges and marker profiles, and their protein components were enriched for cytoskeletal, metabolic, and vesicle-trafficking components relevant to epithelial signaling and immune modulation. Among these proteins, sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) was examined in detail to obtain molecular evidence suggesting its role in sphingolipid metabolism in the parasite. The C. sinensis SMPDL3A (Cs_SMPDL3A) shared the overall structure and core catalytic residues with mammalian homologs, SMPDL3A and sphingomyelin phosphodiesterase 1 (SMPD1), a finding consistent with the possibility that Cs_SMPDL3A may retain authentic sphingomyelinase activity. Although lacking the saponin B domain of SMPD1, Cs_SMPDL3A carries a C-terminal transmembrane segment that may facilitate sphingomyelin access by positioning the enzyme on lipid bilayers. Collectively, these findings suggest that Cs_SMPDL3A participates in host sphingomyelin turnover, potentially generating ceramide for uptake by SMPD1-lacking C. sinensis or contributing to ceramide-associated immune responses in the biliary tract, offering new insight into lipid-centered host–parasite interactions during clonorchiasis.

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