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

Sabine Bachmaier*, Giacomo Giacomelli, Estefanía Calvo-Alvarez, Larissa Rezende Vieira, Jan Van Den Abbeele, Aris Aristodemou, Esben Lorentzen, Matt K. Gould, Ana Brennand, Jean William Dupuy, Ignasi Forné, Axel Imhof, Marc Bramkamp, Didier Salmon, Brice Rotureau, Michael Boshart

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Article number5445
JournalNature Communications
Volume13
Issue1
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2022

Fingerprint

Dive into the research topics of 'A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission'. Together they form a unique fingerprint.

Cite this