A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission

Sabine Bachmaier (1) , Giacomo Giacomelli (1, 2) , Estefanía Calvo-Alvarez (3) , Larissa Rezende Vieira (4) , Jan van den Abbeele (5) , Aris Aristodemou (1) , Esben Lorentzen (6) , Matt Gould (1) , Ana Brennand (1) , Jean-William Dupuy (7) , Ignasi Forné (1) , Axel Imhof (1) , Marc Bramkamp (1, 2) , Didier Salmon (4) , Brice Rotureau (3) , Michael Boshart (1)

1 LMU - Ludwig-Maximilians University [Munich]
2 CAU - Christian-Albrechts-Universität zu Kiel = Christian-Albrechts University of Kiel = Université Christian-Albrechts de Kiel
3 Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology
4 Federal University of Rio de Janeiro
5 ITM - Institute of Tropical Medicine [Antwerp]
6 Aarhus University [Aarhus]
7 Plateforme Protéome [Bordeaux]

Abstract Signaling from ciliary microdomains controls developmental processes in metazoans. Trypanosome transmission requires development and migration in the tsetse vector alimentary tract. Flagellar cAMP signaling has been linked to parasite social motility (SoMo) in vitro, yet uncovering control of directed migration in fly organs is challenging. Here we show that the composition of an adenylate cyclase (AC) complex in the flagellar tip microdomain is essential for tsetse salivary gland (SG) colonization and SoMo. Cyclic AMP response protein 3 (CARP3) binds and regulates multiple AC isoforms. CARP3 tip localization depends on the cytoskeletal protein FLAM8. Re-localization of CARP3 away from the tip microdomain is sufficient to abolish SoMo and fly SG colonization. Since intrinsic development is normal in carp3 and flam8 knock-out parasites, AC complex-mediated tip signaling specifically controls parasite migration and thereby transmission. Participation of several developmentally regulated receptor-type AC isoforms may indicate the complexity of the in vivo signals perceived.

Domaines: Sciences du Vivant [q-bio]

Sabine Bachmaier, Giacomo Giacomelli, Estefanía Calvo-Alvarez, Larissa Rezende Vieira, Jan van den Abbeele, et al.. A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission. Nature Communications, 2022, 13 (1), pp.5445. ⟨10.1038/s41467-022-33108-z⟩. ⟨pasteur-03779404⟩