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Title: Prokineticin receptor identified by phage display is an entry receptor for Trypanosoma cruzi into mammalian cells
Authors: Khusal, Ketna Guilhermino
Tonelli, Renata Rosito [UNIFESP]
Mattos, Eliciane Cevolani
Soares, Chrislaine Oliveira
Di Genova, Bruno Martorelli [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Urias, Úrsula
Colli, Walter
Alves, Maria Julia Manso
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Keywords: Prokineticin-2 receptor
T. cruzi invasion
Phage display
Issue Date: 1-Jan-2015
Publisher: Springer
Citation: Parasitology Research. New York: Springer, v. 114, n. 1, p. 155-165, 2015.
Abstract: Trypanosoma cruzi trypomastigotes invade a great variety of mammalian cells, with several molecules being implicated in this complex event. Herein, the sequence GGIALAG present in prokineticin-2 receptor (PKR2), selected by phage display technology, is described as a new T. cruzi receptor for the Tc85 group of glycoproteins belonging to the gp85/TS superfamily and involved in cellular invasion of mammalian hosts. This finding is confirmed by the inhibitory activity of MCF10-A (human mammary) cell invasion by T. cruzi either by anti-PKR2 antibodies (77 %) or GGIALAG-synthetic peptide (42 %). Furthermore, interference RNA (iRNA) inhibition of PKR2 expression in MCF10-A cells reduces T. cruzi invasion by 50 %. the binding site of Tc85 to PKR2 was localized at the C-terminal end of the molecule, upstream of the conserved FLY sequence, previously implicated in parasite cell invasion. PKR2, a receptor formed by seven membrane-spanning alpha-helical segments, is mainly present in the central nervous system, peripheral organs, and mature blood cells. Due to its wide distribution, PKR2 could be a suitable receptor for T. cruzi natural infection, contributing to the parasite dissemination throughout the mammalian organism. These findings augment the number and diversity of possible in vivo receptors for T. cruzi and reassure the multiplicity of Tc85 binding sites to mammalian hosts.
ISSN: 0932-0113
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