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

Article Article scientifique Article A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages eng 2023-06-16 author Kuehnel Ronja Marie Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 943672 Département de microbiologie et médecine moléculaire (MIMOL) author Ganga Emma Leite Velho 0009-0001-0116-2226 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 974611 Département de microbiologie et médecine moléculaire (MIMOL) author Balestra Aurélia 0000-0001-9934-6404 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 884110 author Suarez Catherine 0000-0003-2984-7881 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 583610 Département de génétique et évolution (Genev) (BIANI) Caty Suarez author Wyss Matthias 0000-0002-6862-0797 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland. author Klages Jemelin Natacha Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 23720 Département de microbiologie et médecine moléculaire (MIMOL) author Brusini Lorenzo 0000-0002-7080-566X Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 929464 Département de microbiologie et médecine moléculaire (MIMOL) author Maco Bohumil 0000-0001-8444-313X Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 863802 Services communs de la faculté de médecine (SCMU) author Brancucci Nicolas 0000-0003-0655-3266 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland. author Voss Till S. 0000-0002-1464-4988 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland. author Soldati-Favre Dominique 0000-0003-4156-2109 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 135114 Département de microbiologie et médecine moléculaire (MIMOL) author Brochet Mathieu 0000-0003-3911-5537 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 12111 Geneva, Switzerland. 843097 Département de microbiologie et médecine moléculaire (MIMOL) eadf2161 10.1126/sciadv.adf2161 37327340 2375-2548 PMC10275601 https://www.science.org/doi/10.1126/sciadv.adf2161 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. Animals Cues Culicidae / parasitology Erythrocytes / parasitology Life Cycle Stages Merozoites / physiology Plasmodium / physiology Dewey 616 Swiss National Science Foundation Regulation of the cGMP/Ca2+ signalling module in malaria parasites 155852 CH Programmes Swiss National Science Foundation Structure-Function Relationship of the Guanylate Cyclase Signaling Platform in Apicomplexa 198545 CH Programmes European Commission Molecular Basis of Toxoplasma gondii Encystation and Persistence 695596 ToxoPersist EU H2020 54 Département de microbiologie et médecine moléculaire 21B false 443 Biologie d'un parasite intracellulaire obligatoire 773 949 Signalisation chez les parasites du paludisme 955 Science advances 9 24 e1fb9368-e781-4f67-8c64-59d1eff0bf69 Article (Published version) Public sciadv.adf2161.pdf 29106152 application/pdf CC BY-NC-4.0 9690ff6d53a40ab6b87a7f8e73e788fa8394e98f4a7d597bab8ae2c94b91e8f6 82cbea0f-b72f-4ec8-8404-7d1f31eb5f7e Appendix Public sciadv.adf2161_sm.pdf 1088026 application/pdf c68b8aab5dbfb07cfa5b893486fa99886f8d56841f2cceea5fbc397f1d4bc4ef 835285fb-7162-4cad-809c-3514ea0c5249 Supplemental data Public sciadv.adf2161_data_s1.zip 2923 application/zip abfa3bb95ff177851f44b4ff51e92017a2278ba3538db8601019f5b2a80c11d4 9b8a6850-1bf4-41d8-a7db-74343b2e4a10 Supplemental data Public sciadv.adf2161_tables_s1_to_s4.zip 138040 application/zip 1a7533acc5bf852b6c58fd73236b9b65ec2e9fbd87b5ea9cc851122c48fee6c8 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

Title	Published in	Year	Views	Downloads

Signalling Pathways and Cytoskeletal Dynamics in Red Blood Cell Egress and Transmission of Plasmodium falciparum		2026	50	0
A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages	Science advances	2023	336	118

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