In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

Abstract

Calcineurin (CaN) is present in all eukaryotic cells, including intracellular trypanosomatid parasites such as Trypanosoma cruzi (Tc) and Leishmania spp. (Lspp). In this study, we performed an in silico analysis of the CaN subunits, comparing them with the human (Hs) and looking their structure, post-translational mechanisms, subcellular distribution, interactors, and secretion potential. The differences in the structure of the domains suggest the existence of regulatory mechanisms and differential activity between these protozoa. Regulatory subunits are partially conserved, showing differences in their Ca2+-binding domains and myristoylation potential compared with human CaN. The subcellular distribution reveals that the catalytic subunits TcCaNA1, TcCaNA2, LsppCaNA1, LsppCaNA1_var, and LsppCaNA2 associate preferentially with the plasma membrane compared with the cytoplasmic location of HsCaNAα. For regulatory subunits, HsCaNB-1 and LsppCaNB associate preferentially with the nucleus and cytoplasm, and TcCaNB with chloroplast and cytoplasm. Calpain cleavage sites on CaNA suggest differential processing. CaNA and CaNB of these trypanosomatids have the potential to be secreted and could play a role in remote communication. Therefore, this background can be used to develop new drugs for protozoan pathogens that cause neglected disease.

The role of Ca2+ in the injury of host cells during the schizogenic stage of E. tenella

“…Furthermore, Ca 2+ plays a crucial role in parasite differentiation, cell scaffold dynamics, migration and colonization and is also a relevant factor in the interaction between the parasite and the host cell ( Docampo and Moreno, 2021 ). The intracellular free Ca 2+ of the host cell increases significantly during the process of host cell development of various intracellular parasites, such as Trypanosoma cruzi, Plasmodium falciparum, Leishmania , and Toxoplasma gondii ( Docampo and Huang, 2021 ; Fu et al, 2021 ; Orrego et al, 2021 ; Scarpelli et al, 2021 ). Therefore, the process of intracellular parasites damaging host cells may be closely related to Ca 2+ signal transduction.…”