Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/46002
SCHISTOSOMA MANSONI VENOM ALLERGEN-LIKE PROTEIN 6 (SMVAL6) MAINTAINS TEGUMENTAL BARRIER FUNCTION
Author
Affilliation
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
University of Texas Southwestern Medical Center. Department of Pharmacology. Dallas, TX, USA.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
University of Texas Southwestern Medical Center. Department of Pharmacology. Dallas, TX, USA.
Aberystwyth University. Institute of Biological, Environmental and Rural Sciences. Aberystwyth, United Kingdom.
Abstract
The Schistosoma mansoni venom allergen-like protein (SmVAL) superfamily is a collection of at least 29
molecules that have been classified into two distinctive groups (Group 1 and Group 2 SmVALs). The fundamental
basis for SmVAL segregation relates to signal peptide and conserved cysteine retention (present
in all Group 1 SmVALs, but absent in all Group 2 SmVALs). These structural differences have led to the
hypothesis that most Group 1 SmVALs, found as components of schistosome excretory/secretory (E/S)
products, predominantly interact with their environment (intermediate or definitive hosts) whereas
the Group 2 SmVALs are retained within the schistosome to fulfil parasite-related functions. While experimental
evidence to support Group 1 SmVAL/host interactions is growing, similar support for identification
of parasite-related Group 2 SmVAL functions is currently lacking. By applying a combination of
approaches to the study of SmVAL6, we provide the first known evidence for an essential function of a
Group 2 SmVAL in schistosome biology. After whole mount in situ hybridisation (WISH) localised
Smval6 to the anterior region of the oesophageal gland (AOG) and cells scattered through the mesenchyme
in adult schistosomes, short interfering RNA (siRNA)-mediated silencing of Smval6 was
employed to assess loss of function phenotypes. Here, siSmval6-mediated knockdown of transcript and
protein levels led to an increase in tegumental permeability as assessed by the quantification of
TAMRA-labelled dextran throughout sub-tegumental cells/tissues. Yeast two hybrid screening using
SmVAL6 as a bait revealed Sm14 (a fatty acid binding protein) and a dynein light chain (DLC) as directly
interacting partners. Interrogation of single-cell RNA-seq (scRNA-seq) data supported these protein interactions
by demonstrating the spatial co-expression of Smval6/dlc/Sm14 in a small proportion of adult cell
types (e.g. neurons, tegumental cells and neoblasts). In silico modelling of SmVAL6 with Sm14 and DLC
provided evidence that opposing faces of SmVAL6 were likely responsible for these protein/protein interactions.
Our results suggest that SmVAL6 participates in oesophageal biology, formation of higher order
protein complexes and maintenance of tegumental barrier function. Further studies of other Group 2
SmVALs may reveal additional functions of this enigmatic superfamily.
Share