A multi-adenylate cyclase regulator at the flagellar tip controls African trypanosome transmission
Open accessPublished version of a preprint
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.
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ColabFold - Making protein folding accessible to all
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- Authors
- Bachmaier, S., Giacomelli, G., Calvo-Alvarez, E., Vieira, L. R., Van Den Abbeele, J., Aristodemou, A., Lorentzen, E., Gould, M. K., Brennand, A., Dupuy, J.-W., Forné, I., Imhof, A., Bramkamp, M., Salmon, D., Rotureau, B., & Boshart, M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Universidade Federal do Rio de Janeiro (BR)
- Aarhus University (DK)
- Université de Bordeaux (FR)
- Inserm (FR)
- Corresponding author
- Bachmaier, Sabine
- Boshart, Michael
- ORCID
- Venue
- Nature Communications
- Published
- 2022-09-16
- Volume
- 13
- Issue
- 1
- Pages
- 5445-5445
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9481589
- OpenAlex
- W4296041492
- Cited by
- 38
- References
- 7
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 17 · 2022: 1
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (acceptedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ludwig-Maximilians-Universität München
- BioNa young scientists award
- IN.WBI excellence fellowship
- Deutsche Forschungsgemeinschaft (443931024)
- Institut Pasteur
- Topics
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- African trypanosomes, Trypanosoma brucei, adenylate cyclase, cAMP signaling, social motility, parasite migration, trypanosome transmission, ciliary signaling
- MeSH terms
- Cyclic AMP, Adenylyl Cyclases, Animals, Trypanosoma, Trypanosoma brucei brucei, Tsetse Flies
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