Figure 2: Schematic overview of signaling pathways identified to date that are involved in gametocyte activation (modified from ). Gametocyte activation is induced by a decrease in temperature and the presence of the mosquito-derived molecule XA. So far, a receptor involved in activation has not been identified. Activation effects PLC and GC, resulting in an increase of IP3 and cGMP. The latter activates a PKG. IP3 mediates release of intracellular calcium from the ER, which activates CDPK4 and consequently Map-2 in the male microgametocyte, eventually leading to exflagellation. A possible link between PKG and calcium release has not yet been confirmed. Signaling pathways in the activated macrogametocyte that are downstream of calcium release were not yet identified. Black lines indicate direct interactions and dashed lines indicate indirect interactions. , calcium ion; CDPK, calcium-dependent protein kinase; cGMP, cyclic guanosine monophosphate; DAG, diacylglycerol; DNA, deoxyribonucleic acid; E, erythrocyte; ER, endoplasmic reticulum; GC, guanylyl cyclase; GTP, guanosine triphosphate; IP3, inositol triphosphate; Map-2, Mitogen-activated protein kinase 2; PDE, phosphodiesterase; PIP2, phosphatidylinositol-4,5-bisphosphate; PKG, cGMP-dependent protein kinase; PLC, phospholipase C; PV, parasitophorous vacuole; R, receptor; T, temperature; XA, xanthurenic acid.