Functional characterisation of a nematode secreted GM2-activator protein

Bruce, Alexandra F.; Gares, Marie-Pierre; Selkirk, Murray E.; Gounaris, Kleoniki

doi:10.1016/j.molbiopara.2006.02.014

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…This parasite GM2AP did not, however, facilitate degradation of GM2 ganglioside by N-acetylhexosaminidase A, although it did inhibit phospholipase D (PLD) activity. Lack of the former activity might be explained by the absence of a domain implicated in binding to hexosaminidase [65]. In this study, we also did not observe hydrolysis of GM2 to GM3 by OvGM2AP, supporting a trend that this activity might be lost in parasitic species.…”

Section: Discussionsupporting

confidence: 74%

Identification and characterization of the Onchocerca volvulus Excretory Secretory Product Ov28CRP, a putative GM2 activator protein

et al. 2019

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Onchocerca volvulus is the nematode pathogen responsible for human onchocerciasis also known as “River blindness”, a neglected tropical disease that affects up to 18 million people worldwide. Helminths Excretory Secretory Products (ESPs) constitute a rich repertoire of molecules that can be exploited for host-parasite relationship, diagnosis and vaccine studies. Here, we report, using a range of molecular techniques including PCR, western blot, recombinant DNA technology, ELISA, high performance thin-layer chromatography and mass spectrometry that the 28 KDa cysteine-rich protein (Ov28CRP) is a reliable component of the O . volvulus ESPs to address the biology of this parasite. We showed that (1) Ov28CRP is a putative ganglioside GM2 Activator Protein (GM2AP) conserved in nematode; (2) OvGM2AP gene is transcriptionally activated in all investigated stages of the parasitic life cycle, including larval and adult stages; (3) The full-length OvGM2AP was detected in in-vitro O . volvulus ESPs of adult and larval stages; (4) the mass expressed and purified recombinant OvGM2AP purified from insect cell culture medium was found to be glycosylated at asparagine 173 and lacked N-terminal signal peptide sequence; (5) the recombinant OvGM2AP discriminated serum samples of infected and uninfected individuals; (6) OvGM2AP competitively inhibits MUG degradation by recombinant β-hexosaminidase A but not MUGS, and could not hydrolyze the GM2 to GM3; (7) humoral immune responses to the recombinant OvGM2AP revealed a negative correlation with ivermectin treatment. Altogether, our findings suggest for the first time that OvGM2AP is an antigenic molecule whose biochemical and immunological features are important to gain more insight into our understanding of host-parasite relationship, as well as its function in parasite development at large.

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Section: Discussionsupporting

confidence: 74%

Identification and characterization of the Onchocerca volvulus Excretory Secretory Product Ov28CRP, a putative GM2 activator protein

et al. 2019

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“…Apparently unrelated to its GM2 transfer property is the function of the GM2 activator as adipokine [ 263 ]. GM2-activator orthologs might serve different functions in other organisms, for example as a pheromone-binding protein in Drosophila [ 264 ], or an inhibitor of PAF-induced chemotaxis in nematodes [ 265 ].…”

Section: Degradationmentioning

confidence: 99%

Ganglioside Biochemistry

2012

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“…GM2‐activator orthologs might serve different functions in other organisms. In Drosophila , a homologous proteins acts as a pheromone binding protein [189], and in a nematode, Trichinella spiralis , a secreted protein apparently without the domain required for binding to hexosaminidase does not stimulate GM2‐degradation by β‐hexosaminidase A, but inhibits PAF‐induced chemotaxis [190].…”

Section: Functional Aspects Of Membrane Lipid Sorting In the Endocytimentioning

confidence: 99%

Lysosomal degradation of membrane lipids

2009

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The constitutive degradation of membrane components takes place in the acidic compartments of a cell, the endosomes and lysosomes. Sites of lipid degradation are intralysosomal membranes that are formed in endosomes, where the lipid composition is adjusted for degradation. Cholesterol is sorted out of the inner membranes, their content in bis(monoacylglycero)phosphate increases, and, most likely, sphingomyelin is degraded to ceramide. Together with endosomal and lysosomal lipid‐binding proteins, the Niemann–Pick disease, type C2‐protein, the GM2‐activator, and the saposins sap‐A, ‐B, ‐C, and ‐D, a suitable membrane lipid composition is required for degradation of complex lipids by hydrolytic enzymes.

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Functional characterisation of a nematode secreted GM2-activator protein

Cited by 13 publications

References 30 publications

Identification and characterization of the Onchocerca volvulus Excretory Secretory Product Ov28CRP, a putative GM2 activator protein

Identification and characterization of the Onchocerca volvulus Excretory Secretory Product Ov28CRP, a putative GM2 activator protein

Ganglioside Biochemistry

Lysosomal degradation of membrane lipids

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