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Screening of ligands for seven transmembrane domain receptor candidates in the parasite Plasmodium falciparum.

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Author(s):
Alexandre Budu
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Celia Regina da Silva Garcia; Maria Regina D'Imperio Lima; Claudio Romero Farias Marinho; Deborah Schechtman; Aline Maria da Silva
Advisor: Celia Regina da Silva Garcia
Abstract

The malaria parasite P. falciparum perceives its milieu and elaborates adequate intracellular responses, that involve protein secretion, growth and cell differentiation. Factors related to second messengers generation and effectors of cell signaling are described in the literature. However, the function of receptors responsible for stimulus perception remains elusive. The in silico identification of putative seven transmembrane receptors in the Plasmodium falciparum genome allowed the exploration of their function. In the thesis, two putative receptors were characterized, PFSR10 and PFSR25. The proteic expression of the receptors was demonstrated in erythrocytic stages of P. falciparum. The receptors have putative interaction partners that participate in cellular functions such as invasion, exocytosis and endocytosis.The receptors were transfected in mammalian cells and, through high-throughput calcium dynamics assays, it is suggested that PFSR10 codes for a receptor that participates in extracellular ATP perception and that PFSR25 codes for a KCl sensor. It is also suggested that KCl modulates cytosolic calcium in response to KCl and that knockout parasites for PFSR25 are incapable of modulating cytosolic calcium in response to KCl. (AU)