Figure 1.

Ca²⁺-dependent signaling pathway in Plasmodium species. Ca²⁺ inside the cytoplasm of parasite controls important processes for parasite survival, such as gliding motility, mediated by activation of PfCaM/PfPKB complex and following phosphorylation of the IMC member protein, GAP45. Additionally, centrins, CDPKs activation, activation of ookinetes and gametocytes are described as Ca²⁺-regulated. A GPCR-like protein, named as PfSR25, has been described as potential regulator in Ca²⁺ homeostasis in malaria parasites, depending on availability of potassium (K⁺) and mediated by IP3 signaling. Melatonin was also described as a trigger for IP3 dependent pathways. Endoplasmic Reticulum (ER) is reported as the major storage of Ca²⁺ and the uptake of this ion possibly depends on SERCA-type Ca²⁺-ATPases. Ca²⁺ discharge depends on receptors activated by IP3, nonetheless, an IP3R remains to be discovered in Plasmodium species. The presence of V-ATPase and VP1 on the food vacuole and acidocalcisome membranes are related to the Ca²⁺ uptake upon an acidic environment maintenance. Acidocalcisome could also have an IP3R that allows exit of Ca²⁺. Calcium can also enter in mitochondria through Ca²⁺/H⁺ antiporter called PfCHA/PfCAX. Activation of PKA and PKG, by cAMP and cGMP, respectively, generated by adenylyl-cyclase (AC) and guanylyl-cyclase (GC), respectively, could also participate in Ca²⁺ homeostasis, however the membrane receptors that stimulate theses pathways remains to be elucidated. Still, upon HCO₃¯ activation, AC can also stimulate Epac activation by cAMP, triggering IP3 signaling through PLC activation. Additionally, a cross-talk among kinases are also proposed to be associated to the merozoite egress mediated by proteolytic cascade events.