A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages

Sci Adv. 2023 Jun 16;9(24):eadf2161. doi: 10.1126/sciadv.adf2161. Epub 2023 Jun 16.


Critical events in the life cycle of malaria-causing parasites depend on cyclic guanosine monophosphate homeostasis by guanylyl cyclases (GCs) and phosphodiesterases, including merozoite egress or invasion of erythrocytes and gametocyte activation. These processes rely on a single GCα, but in the absence of known signaling receptors, how this pathway integrates distinct triggers is unknown. We show that temperature-dependent epistatic interactions between phosphodiesterases counterbalance GCα basal activity preventing gametocyte activation before mosquito blood feed. GCα interacts with two multipass membrane cofactors in schizonts and gametocytes: UGO (unique GC organizer) and SLF (signaling linking factor). While SLF regulates GCα basal activity, UGO is essential for GCα up-regulation in response to natural signals inducing merozoite egress and gametocyte activation. This work identifies a GC membrane receptor platform that senses signals triggering processes specific to an intracellular parasitic lifestyle, including host cell egress and invasion to ensure intraerythrocytic amplification and transmission to mosquitoes.

MeSH terms

  • Animals
  • Cues
  • Culicidae* / parasitology
  • Erythrocytes / parasitology
  • Life Cycle Stages
  • Merozoites / physiology
  • Plasmodium* / physiology