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

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  • Sabine Bachmaier, Ludwig Maximilian University
  • ,
  • Giacomo Giacomelli, Ludwig Maximilian University
  • ,
  • Estefanía Calvo-Alvarez, Université de Paris
  • ,
  • Larissa Rezende Vieira, Universidade Federal do Rio de Janeiro
  • ,
  • Jan Van Den Abbeele, Institute of Tropical Medicine Antwerp
  • ,
  • Aris Aristodemou, Ludwig Maximilian University
  • ,
  • Esben Lorentzen
  • Matt K. Gould, Ludwig Maximilian University
  • ,
  • Ana Brennand, Ludwig Maximilian University
  • ,
  • Jean William Dupuy, Universite Bordeaux
  • ,
  • Ignasi Forné, Ludwig Maximilian University
  • ,
  • Axel Imhof, Ludwig Maximilian University
  • ,
  • Marc Bramkamp, Ludwig Maximilian University
  • ,
  • Didier Salmon, Universidade Federal do Rio de Janeiro
  • ,
  • Brice Rotureau, Université de Paris
  • ,
  • Michael Boshart, Ludwig Maximilian University

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
Publication statusPublished - Dec 2022

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