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Elucidation of signaling and functional activities of serpentine receptors, PfSR12 and PfSR25

Grant number: 09/07155-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2009
Effective date (End): July 31, 2013
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Célia Regina da Silva Garcia
Grantee:Miriam Santos de Moraes
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:11/51295-5 - Functional genomics in Plasmodium, AP.TEM

Abstract

Malaria is the major human parasitic disease. A recent study revealed over 500 million of clinical cases of P. falparum malaria worldwide. The control of this disease has long been a problem, despite intense research efforts, possibly because of the complex biology of Plasmodium, and the ability of this organism to conceal itself within host cells. The symptomatic stage of malaria infection concurs with the development of the asexual cycle of the parasites in the red blood cell. Analysis of P. falciparum gene expression profiles revealed that a programmed cascade of cellular processes ensures completion of the parasite´s intraerythrocytic developmental cycle. An emerging series of data are now accumulating concerning the effectors of second messengers such as Ca2+-activated proteases, cAMP-dependent kinases, Ca2+-dependent kinases and metabolic enzyme effectors. The question the arises: how woul parasites sense the environment to activate signaling machineries responsible for the control of their growth and differentiation?By using real-time PCR we found that all four predicted serpentine receptors are transcribed and differentially regulated during the assexual intraerythrocytic cycle of P. falciparum. Moreover, PfSR25 is expressed in gametocytes and sprozoites. Altogether, these data suggest that the putative serpentine receptors might have distinct functions required during specific stages of the life cycle. Because no ligands have been described for PfSR, the signaling pathways for receptor activation as well as the functions of the receptor are largely unknown. Functional expression of codon-optmized PfSR12 and PfSR25 in a variety of heterologous systems would illuminate the potential function of PfSR12 and PfSR25. To further analyse these putative receptors, specific antisera were generated and used in immunoblot and imunofluorescence analyses of P. falciparum-infected RBCs e HEK293 cells. Functional characterization of these receptors may reveal future pharmacological targets.