Sm21.6 a novel EF-hand family protein member located on the surface of Schistosoma mansoni adult worm that failed to induce protection against challenge infection but reduced liver pathology

Lopes, Débora de Oliveira; Paiva, Leonardo F.; Martins, Maurício A.; Cardoso, Fernanda C.; Rajão, Matheus Andrade; Pinho, J. M. R.; Caliari, Marcelo Vidigal; Correa-Oliveira, Rodrigo; Mello, Samantha M.; Leite, Luciana C. C.; Oliveira, Sérgio C.

doi:10.1016/j.vaccine.2009.04.068

Cited by 27 publications

(26 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While many of the proteins have been localised to the tegument of the worm, their in vivo functions have not been elucidated (Fitzsimmons, et al, 2012, Havercroft, et al, 1990, Huang, et al, 2007, Kim, et al, 2012, Lopes, et al, 2009, Mohamed, et al, 1998, Subpipattana, et al, 2012, Xu, et al, 2014, Zhang, et al, 2012. From the available data it is evident that, despite clear sequence similarities, differences exist between the proteins at the biochemical level.…”

Section: Introductionmentioning

confidence: 99%

FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains

Cheung

Thomas

Timson

2016

Experimental Parasitology

View full text Add to dashboard Cite

FH22 has been previously identified as a calcium-binding protein from the common liver fluke, Fasciola hepatica. It is part of a family of at least four proteins in this organism which combine an EFhand containing N-terminal domain with a C-terminal dynein light chainlike domain. Here we report further biochemical properties of FH22, which we propose should be renamed FhCaBP1 for consistency with other family members. Molecular modelling predicted that the two domains are linked by a flexible region and that the second EF-hand in the N-terminal domain is most likely the calcium ion binding site. Native gel electrophoresis demonstrated that the protein binds both calcium and manganese ions, but not cadmium, magnesium, strontium, barium, cobalt, copper(II), iron (II), nickel, zinc, lead or potassium ions. Calcium ion binding alters the conformation of the protein and increases its stability towards thermal denaturation. FhCaBP1 is a dimer in solution and calcium ions have no detectable effect on the protein's ability to dimerise. FhCaBP1 binds to the calmodulin antagonists trifluoperazine and chlorpromazine. Overall, the FhCaBP1's biochemical properties are most similar to FhCaBP2 a fact consistent with the close sequence and predicted structural similarity between the two proteins. properties are most similar to FhCaBP2 a fact consistent with the close sequence and predicted structural similarity between the two proteins.

show abstract

Section: Introductionmentioning

confidence: 99%

FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains

Cheung

Thomas

Timson

2016

Experimental Parasitology

View full text Add to dashboard Cite

show abstract

“…antigens, such as Sm22.6, Sm29, Sm21.6, and Sm14, are associated with resistance to infection and/or reduction of morbidity. [9][10][11][12] These particular proteins are found mainly in the tegument of S. mansoni, and induce high levels of IL-4, IL-10, and IFN-g production that exert partial protection against experimental S. mansoni infection. 13 Additionally, a fraction of S. mansoni soluble adult worm antigen (SWAP) known as PIII is able to induce protection against a challenge infection after immunization in a murine model of schistosomiasis.…”

Section: Introductionmentioning

confidence: 99%

Factors Associated with Resistance to Schistosoma mansoni Infection in an Endemic Area of Bahia, Brazil

Oliveira¹,

Figueiredo²,

Cardoso³

et al. 2012

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Detailed knowledge of factors associated with resistance to Schistosoma mansoni infection in endemic areas might facilitate more effective schistosomiasis control. We conducted a cross-sectional study of persons resistant to schistosomiasis and found no association between socioeconomic status and resistance to infection. Mononuclear cells of resistant subjects produced higher levels of interleukin-5 (IL-5), IL-13 and interferon-g upon stimulation with soluble egg antigen (SEA) compared with infected persons. When stimulated with Sm21.6 or Sm22.6, levels of IL-10 were higher in cell culture of resistant persons. Levels of IgE against soluble adult worm antigen (SWAP) and against interleukin-4-inducing principle from S. mansoni eggs (IPSE) and levels of IgG4 against SWAP, SEA, and Sm22.6 were lower in the resistant group compared with the susceptible group. Our data suggest that socioeconomic status could not fully explain resistance to S. mansoni infection observed in the studied area. However, a mixture of Th1 and Th2 immune responses and low levels of specific IgG4 against parasite antigens could be mediating resistance to infection.

show abstract

“…The expression patterns of SmTAL10 and SmTAL11 (Fitzsimmons et al, 2012) indicate that they are highly expressed in adult stages. Sm21.6 (SmTAL8) was localised predominately to the tegument (Lopes et al, 2009), although given the magnification used in that paper, the exact localisation in the tegument remains uncertain and has not as yet been confirmed. Unfortunately, the results from crosslinking and BN-PAGE could not be validated by immunoprecipitation methods.…”

Section: Discussionmentioning

confidence: 83%

“…The most comprehensive report of the expression profile of SmTALs in life cycle stages come from microarray data (Fitzsimmons et al, 2012 and Strand, 1996;Li et al, 2000;Lopes et al, 2009;Mohamed et al, 1998;Zhang et al, 2005). Although immunofluorescence has been used for high resolution studies of the cellular distribution of many molecules, in schistosome biology the method has not reached its potential, possibly due to the small size of the apical cytoplasm of the tegument (which is 5 microns thick), and the multi-faceted membrane system that occurs in this cytoplasmic membrane.…”

Section: Discussionmentioning

confidence: 99%

“…In S. mansoni the TALs named by their molecular weight, Sm20.8, Sm21.7 and Sm22.6, are well characterised (Francis and Bickle, 1992;Hoffmann and Strand, 1997;Jeffs et al, 1991;Mohamed et al, 1998;Webster et al, 1996). Recently, another TAL, Sm21.6, was identified (Lopes et al, 2009). A total of 13 TALs have been found in the S. mansoni genome each having a different life cycle expression pattern and antibody responses (Fitzsimmons et al, 2012).…”

Section: Schistosome Tegument Allergen-like Antigensmentioning

confidence: 99%

See 1 more Smart Citation

Molecular interactions of proteins associated with surface membrane biogenesis and renewal in the tegument of Schistosoma mansoni

Schulte¹

View full text Add to dashboard Cite

The tegument of Schistosoma mansoni serves a variety of critical biological roles for the parasite, including uptake of nutrients, osmoregulation, immune evasion and immunomodulation. Dynein light chains (DLCs) and tetraspanins (TSPs) are prominent proteins in the tegument and appear to be intimately linked with other molecules present in the apical, host-interactive, membrane of the parasites. In other eukaryotic cells, cytoplasmic DLCs are a subunit of motor complexes involved in such diverse cellular translocation events as protein trafficking, mitosis and ciliary beating. DLCs of the schistosome tegument likely have similar roles and are likely to be important in the development and renewal of the tegument membrane, thereby contributing to parasite survival in its host. There is evidence that S. mansoni DLCs bind to a group of proteins unique to the tegument, the tegument allergen-like antigens (TALs) suggesting that schistosome DLCs may form complexes outside of the dynein complex. TSPs are membrane-spanning proteins that act as scaffolds for the formation of membraneassociated protein complexes comprising a wide variety of proteins. These TSP-enriched microdomains are known to play a wide range of roles within human cells, including maintenance of cell morphology and cell signalling.The biology of DLCs, TALs and TSPs in schistosome tegument is investigated in this study. Two DLCs, SmDLC1 and SmDLC5, three TALs, Sm20.8, Sm21.7 and Sm22.6 along with SmTSP-2 are the focus of this study. The tegumental localisation and transcription throughout the schistosome life cycle are reported for each transcript. By indirect immunocytochemistry the localisation within the tegument of SmTSP-2, SmDLC1 and Sm22.6 was investigated using parasites prepared by high pressure freezing for electron microscopy and cryosubstitution in uranyl acetate in solvent. SmTSP-2 was strongly membrane associated but little labelling was associated with the apical tegument membranes. SmDLC1 labelling was abundant in the entire tegument cytoplasm, close to the apical tegument membranes, surface invaginations and on the membranes on some tegumental vesicles. Sm22.6 had a more diffuse localisation pattern across the cytoplasm and labelling was apparent close to the apical surface membranes. Dual labelling immunocytochemistry of SmDLC1 and Sm22.6 did not show labelling patterns that confirmed the interaction of these SmDLCs and SmTALs. The transcript abundance of SmDLCs and SmTALs were assessed in the schistosome life cycle by real-time PCR. A similar pattern was seen for most transcripts, with transcript abundance increasing as the parasite developed from free-living life cycle stages (egg, miracidia, cercariae) to parasitic ii stages (schistosomula and adults). The most striking exception to this pattern is Sm21.7, which has a consistently high abundance across all life cycle stages.Protein interactions in the tegument were explored using Blue Native polyacrylamide gel electrophoresis and protein crosslinkers, coupled with in-line liqui...

show abstract

Sm21.6 a novel EF-hand family protein member located on the surface of Schistosoma mansoni adult worm that failed to induce protection against challenge infection but reduced liver pathology

Cited by 27 publications

References 29 publications

FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains

FhCaBP1 (FH22): A Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains

Factors Associated with Resistance to Schistosoma mansoni Infection in an Endemic Area of Bahia, Brazil

Molecular interactions of proteins associated with surface membrane biogenesis and renewal in the tegument of Schistosoma mansoni

Contact Info

Product

Resources

About