Fasciclin-calcareous corpuscle binary complex mediated protein-protein interactions in Taenia solium metacestode

Abstract

BackgroundNeurocysticercosis (NC) caused by Taenia solium metacestode (TsM) is a serious neurological disease of global concern. Diverse bioactive molecules involved in the long-term survival of TsM might contribute to disease progression. Fasciclin (Fas) is an extracellular protein that mediates adhesion, migration and differentiation of cells by interacting with other molecules. We hypothesized that TsMFas might bind to calcareous corpuscle (CC) through its adhesive property and participate in crucial protein-protein interactions, thus contributing to the creation of a symbiotic interactome network.MethodsTwo paralogous TsMFas (TsMFas1 and TsMFas2) were isolated, and their molecular properties were characterized. The co-localization pattern of TsMFas1 and TsMFas2 with CC was determined. CC-TsMFas binary complex was generated by incubating CC with recombinant proteins (rTsMFas1 and 2). In vitro binding assay of CC-rTsMFas1 or CC-rTsMFas2 binary complex with TsM cellular proteins extracted from scolex and neck was conducted. Their binding partners were identified through proteomic analysis. Integrated protein-protein interaction networks were established.Results TsMFas1 (6072 bp long) was composed of 15 exons (841 amino acid polypeptide) interrupted by 14 introns. TsMFas2 (5201 bp long) comprised of 11 exons (597 amino acids) and 10 intervening introns. These proteins displayed 22% amino acid sequence identity to each other, but tightly conserved Fas-related domains. Several isoforms of Fas1 and Fas2 proteins might have been expressed through post-translational modifications. They showed adhesion activity with other cells. TsMFas proteins were largely distributed in parenchymal regions of the scolex and bladder wall. These molecules were co-localized with CC, a unique organelle found in platyhelminths. Subsequent proteome analysis of CC-Fas binary complex mediated protein-protein interactions revealed seven protein ligands in the TsM cellular proteins. Their functions were mainly segregated into carbohydrate metabolism (enolase, phosphoenolpyruvate carboxykinase, phosphoglycerate kinase and glyceraldehyde 3-phosphate dehydrogenase) and cytoskeleton/cellular motility (actin, paramyosin and innexin nuc-9). Those proteins had direct (physical) and/or indirect (functional) relationships along with their biochemical properties and biological roles.ConclusionProtein repertoires strongly suggest that TsMFas and CC may symbiotically mediate protein-protein interactions during biological processes to maintain efficacious homeostatic functions and ensure the prolonged survival of TsM in the host.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2359-2) contains supplementary material, which is available to authorized users.

Targeted and non-targeted proteomics to characterize the parasite proteins of Echinococcus multilocularis metacestodes

“…All AgB subunits localized to the surface of the calcareous corpuscles in the metacestodes, as observed previously in cysts ex vivo from infected rats ( Rickard et al., 1977 ). Fasciclin, another calcareous corpuscle-associated protein, was shown to ensure survival of the cestode Taenia solium in the host ( Ahn et al., 2017a ). It is important to note that the here-described antisera against the five polypeptides of AgB might be cross-reacting due to high antigen sequence homology, and thus, no individual interpretations can be made, even though our analyses did reveal only cross-reactivity between the AgB8/2 antiserum and the AgB8/5 polypeptide.…”

Evolutionary Adaptations of Parasitic Flatworms to Different Oxygen Tensions

“…In parasitic flatworms, the presence of various families of transporters specialized in the removal of metabolites and drugs has been reported. Although this representation is not homogeneous in flatworms, its participation in detoxification processes has been demonstrated [ 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 ]. In a previous experiment, we inhibited the TGR enzyme activity of T. crassiceps cysticerci under in vitro conditions and observed the appearance of GSSG in the culture medium, which led to the proposition that the cestode expels GSSG excess as a mechanism to avoid the change of the redox environment inside [ 165 ].…”

Advances in Serological Diagnosis of Taenia solium Neurocysticercosis in Korea

“…The expression pattern of these molecules in the scolex was also found to be related to the antibody reactivity that culminated in chronic cases, as evidenced by endophilin B1 [39]. In addition, TsMFas molecules bound to calcareous corpuscles may symbiotically mediate protein-protein interactions governing carbohydrate-metabolizing enzymes and cytoskeleton/cell motility to maintain efficacious homeostatic functions and ensure the prolonged survival of the TsM in the host [26].…”

“…Safe and effective chemotherapeutics for the medical treatment of NC were successfully launched [22,23]. Several molecular and cell biological studies have elucidated bioactive molecules of TsM that are crucially involved in the regulation of homeostatic functions [24,25] and the symbiotic protein interactome network of the worm [26]. These efforts have made the disease controllable and manageable.…”