Decoding the role and the signaling pathway activated by the Plasmodium falciparum SR12 GPCR- like receptor

Malaria causes millions of deaths worldwide and is considered a huge public health problem for underdeveloped countries. Based on the complete DNA sequence analysis of the P. falciparum genome, Prof. Celia’s group revealed four putative serpentine receptors – PfSR1, PfSR10, PfSR12, and PfSR25 – that have a membrane topology similar to that of GPCRs, having seven predicted transmembrane domain (7TM) receptors. It was reported that one of these GPCR-like proteins, P. falciparum serpentine receptor 12 (PfSR12), acts as a chaperone and increases the expression of several GPCRs resulting in increased responsiveness to various hormones of mammalian cells that could contribute to the deleterious effects of Plasmodium falciparum infection. Western-blot and Real-time PCR analysis showed that PfSR12 is expressed from late trophozoite to schizont stages. Since the mechanisms and the proteins involved in GPCR signal transduction in P. falciparum are not clear and in order to understand how the receptors PfSR12 works, its function was studied in a cellular model where GPCR signaling processes are well understood and for which tools are readily available. Mammalian cell cultures and BRET-based biosensors will therefore be the main model systems. Given that GPCRs represent highly druggable targets targeting PfSR12 may represent a promising way for developing new antimalarial drugs.

Project details

Basic Science

Nov 2020

Brazil