Flagellar motility is required for the viability of the bloodstream trypanosome

Richard Broadhead, Helen R. Dawe, Helen Farr, Samantha Griffiths, Sarah R. Hart, Neil Portman, Michael K. Shaw, Michael L. Ginger, Simon J. Gaskell, Paul G. McKean, Keith Gull

Research output: Contribution to journalArticle

333 Citations (Scopus)

Abstract

The 9+2 microtubule axoneme of flagella and cilia represents one of the most iconic structures built by eukaryotic cells and organisms. Both unity and diversity are present among cilia and flagella on the evolutionary as well as the developmental scale. Some cilia are motile, whereas others function as sensory organelles and can variously possess 9+2 and 9+0 axonemes and other associated structures1. How such unity and diversity are reflected in molecular repertoires is unclear. The flagellated protozoan parasite Trypanosoma brucei is endemic in sub-Saharan Africa, causing devastating disease in humans and other animals2. There is little hope of a vaccine for African sleeping sickness and a desperate need for modern drug therapies 3. Here we present a detailed proteomic analysis of the trypanosome flagellum. RNA interference (RNAi)-based interrogation of this proteome provides functional insights into human ciliary diseases and establishes that flagellar function is essential to the bloodstream-form trypanosome. We show that RNAi-mediated ablation of various proteins identified in the trypanosome flagellar proteome leads to a rapid and marked failure of cytokinesis in bloodstream-form (but not procyclic insect-form) trypanosomes, suggesting that impairment of flagellar function may provide a method of disease control. A postgenomic meta-analysis, comparing the evolutionarily ancient trypanosome with other eukaryotes including humans, identifies numerous trypanosome-specific flagellar proteins, suggesting new avenues for selective intervention.

LanguageEnglish
Pages224-227
Number of pages4
JournalNature
Volume440
Issue number7081
DOIs
Publication statusPublished - 9 Mar 2006
Externally publishedYes

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Trypanosomiasis
Flagella
Cilia
Axoneme
Proteome
RNA Interference
African Trypanosomiasis
Trypanosoma brucei brucei
Cytokinesis
Africa South of the Sahara
Eukaryotic Cells
Eukaryota
Microtubules
Organelles
Proteomics
Insects
Meta-Analysis
Parasites
Proteins
Vaccines

Cite this

Broadhead, R., Dawe, H. R., Farr, H., Griffiths, S., Hart, S. R., Portman, N., ... Gull, K. (2006). Flagellar motility is required for the viability of the bloodstream trypanosome. Nature, 440(7081), 224-227. https://doi.org/10.1038/nature04541
Broadhead, Richard ; Dawe, Helen R. ; Farr, Helen ; Griffiths, Samantha ; Hart, Sarah R. ; Portman, Neil ; Shaw, Michael K. ; Ginger, Michael L. ; Gaskell, Simon J. ; McKean, Paul G. ; Gull, Keith. / Flagellar motility is required for the viability of the bloodstream trypanosome. In: Nature. 2006 ; Vol. 440, No. 7081. pp. 224-227.
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Broadhead, R, Dawe, HR, Farr, H, Griffiths, S, Hart, SR, Portman, N, Shaw, MK, Ginger, ML, Gaskell, SJ, McKean, PG & Gull, K 2006, 'Flagellar motility is required for the viability of the bloodstream trypanosome', Nature, vol. 440, no. 7081, pp. 224-227. https://doi.org/10.1038/nature04541

Flagellar motility is required for the viability of the bloodstream trypanosome. / Broadhead, Richard; Dawe, Helen R.; Farr, Helen; Griffiths, Samantha; Hart, Sarah R.; Portman, Neil; Shaw, Michael K.; Ginger, Michael L.; Gaskell, Simon J.; McKean, Paul G.; Gull, Keith.

In: Nature, Vol. 440, No. 7081, 09.03.2006, p. 224-227.

Research output: Contribution to journalArticle

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Broadhead R, Dawe HR, Farr H, Griffiths S, Hart SR, Portman N et al. Flagellar motility is required for the viability of the bloodstream trypanosome. Nature. 2006 Mar 9;440(7081):224-227. https://doi.org/10.1038/nature04541