Prokineticin receptor identified by phage display is an entry receptor for Trypanosoma cruzi into mammalian cells

Prokineticin receptor identified by phage display is an entry receptor for Trypanosoma cruzi into mammalian cells

Author Khusal, Ketna Guilhermino Google Scholar
Tonelli, Renata Rosito Autor UNIFESP Google Scholar
Mattos, Eliciane Cevolani Google Scholar
Soares, Chrislaine Oliveira Google Scholar
Di Genova, Bruno Martorelli Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Urias, Úrsula Google Scholar
Colli, Walter Google Scholar
Alves, Maria Julia Manso Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
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.
Keywords Prokineticin-2 receptor
T. cruzi invasion
Phage display
iRNA
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2012/50188-3
Date 2015-01-01
Published in Parasitology Research. New York: Springer, v. 114, n. 1, p. 155-165, 2015.
ISSN 0932-0113 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 155-165
Origin http://dx.doi.org/10.1007/s00436-014-4172-6
Access rights Closed access
Type Article
Web of Science ID WOS:000347158100017
URI http://repositorio.unifesp.br/handle/11600/38572

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