Authors: K G Khusal R R Tonelli E C Mattos C O Soares B M Di Genova M A Juliano U Urias W Colli M J M Alves
Publish Date: 2014/10/17
Volume: 114, Issue: 1, Pages: 155-165
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 prokineticin2 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 MCF10A human mammary cell invasion by T cruzi either by antiPKR2 antibodies 77 or GGIALAGsynthetic peptide 42 Furthermore interference RNA iRNA inhibition of PKR2 expression in MCF10A cells reduces T cruzi invasion by 50 The binding site of Tc85 to PKR2 was localized at the Cterminal end of the molecule upstream of the conserved FLY sequence previously implicated in parasite cell invasion PKR2 a receptor formed by seven membranespanning αhelical 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 hostsThis work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo FAPESP grant 2012/501883 and Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq We are indebted to Drs Renata Pasqualini and Ricardo Giordano for kindly providing the CX7Cphage display library to Dr Richard Garratt for helpful discussions and to Dr Ricardo Giordano for critically reading the manuscript
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