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

Sabine Bachmaier, Giacomo Giacomelli, Estefania Calvo-Alvarez, Larissa Rezende Vieira, Jan Van Den Abbeele, Aris Aristodemou, Esben Lorentzen, Matthew Gould, Ana Brennand, Jean-Wiliam Dupuy, Ignasi Forne, Axel Imhof, Marc Bramkamp, Didier Salmon, Brice Rotureau, Michael Boshart

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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.

Original languageEnglish
Article number5445
JournalNature Communications
Issue number1
Pages (from-to)5445
Number of pages17
Publication statusPublished - 2022


  • Adenylyl Cyclases/metabolism
  • Animals
  • Cyclic AMP
  • Trypanosoma
  • Trypanosoma brucei brucei/metabolism
  • Tsetse Flies/parasitology


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