Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4694333
Author(s)
Kuehnel, R. M.; Ganga, E.; Balestra, A. C.; Suarez, C.; Wyss, M.; Klages, N.; Brusini, L.; Maco, B.; Brancucci, N.; Voss, T. S.; Soldati, D.; Brochet, M.
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 GCalpha, 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 GCalpha basal activity preventing gametocyte activation before mosquito blood feed. GCalpha interacts with two multipass membrane cofactors in schizonts and gametocytes: UGO (unique GC organizer) and SLF (signaling linking factor). While SLF regulates GCalpha basal activity, UGO is essential for GCalpha 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.
