INVESTIGADORES
DE MIGUEL Natalia
congresos y reuniones científicas
Título:
Functional analyses of the Tetraspanin 6 membrane protein during Trichomonas vaginalis migration and pathogenesis
Autor/es:
NATALIA DE MIGUEL
Lugar:
Woods Hole
Reunión:
Congreso; XX Molecular Parasitology Meeting; 2009
Resumen:
The unicellular parasitic Trichomonas vaginalis is the causative
agent of trichomoniasis, the most
prevalent non-viral sexually transmitted disease in humans. Because T. vaginalis is an obligate
extracellular pathogen, proteins on the surface may play a critical role host-parasite
interaction and the consequent pathogenesis. Here, we report the identification
and functional characterization of T.
vaginalis Tetraspanin-6 (TSP6). TSP6 is member of the tetraspanin family,
which comprises a large superfamily of cell surface-associated membrane
proteins that has been implicated in fundamental biological processes,
including cell adhesion, migration, fusion and proliferation.
Our
studies showed that TSP6 targets to both the plasma membrane and the flagella
of free living parasites. The protein relocalizes during exposure to vaginal epithelial cells (VECs). Moreover,
qPCR analysis of parasites exposed to VECs revealed a dual upregulation over
the time. The complex localization and expression pattern of TSP6 suggests that
its intracellular trafficking and distribution must be tightly regulated during
parasite pathogenesis. In order to evaluate TSP6 function, cell adhesion and
migration assays were performed using parasites that over-express full length
and C-terminal truncated version of TSP6. Although no effect was observed on
parasite that overexpress full length TSP6, when the C-terminal tail is
removed (TSP6DCt), exogenous TSP6 exerted a dominant negative effect, as it significantly
reduced migration through matrigel invasion chambers compared with parasites
transfected with empty plasmid. No effect was observed in adhesion experiments.
In addition, TSP6DCt does not relocalize upon exposure to VECs as observed for
the full length protein. In conclusion, TSP6 appears to influence cellular
migration, with the TSP6 tail being of particular importance in determining the
outside-in signals that follow ligand engagement. The elucidation of
determinants involved in the process of migration may reveal virulence factors
and novel therapeutic targets to combat disease.