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Swimming with protists: perception, motility and flagellum assembly

Key Points

  • Flagella and cilia are used in unicellular and multicellular eukaryotes for fast cell motility, rapid movement of material over cell surfaces, cell feeding and cell division.

  • The structure of the eukaryotic flagellum is not related to the structure of the prokaryotic flagellum. The principal feature of most motile eukaryotic flagella is the '9+2' microtubule axoneme. Some deviations from this canonical structure are known.

  • Recent biochemical and proteomic studies have identified protist flagella as organelles with their own associated metabolism. The challenge is to understand the physiological functions of these unexpected metabolic pathways.

  • Intraflagellar transport is a widely conserved mechanism by which flagella in many organisms are built. For some protists, studies in the areas of cell biology and comparative genomics are challenging our paradigms of flagellum assembly.

  • Protist flagella also function in response to, and in the initiation of, signal-transduction cascades.

  • Flagellar or ciliary motility is important for cytokinesis in some protists. In the example of the African trypanosome, Trypanosoma brucei, small-molecule-dependent intervention could eventually afford new possibilities for drug design against sleeping sickness, a tropical disease of Sub-Saharan Africa.

Abstract

In unicellular and multicellular eukaryotes, fast cell motility and rapid movement of material over cell surfaces are often mediated by ciliary or flagellar beating. The conserved defining structure in most motile cilia and flagella is the '9+2' microtubule axoneme. Our general understanding of flagellum assembly and the regulation of flagellar motility has been led by results from seminal studies of flagellate protozoa and algae. Here we review recent work relating to various aspects of protist physiology and cell biology. In particular, we discuss energy metabolism in eukaryotic flagella, modifications to the canonical assembly pathway and flagellum function in parasite virulence.

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Figure 1: Flagellate diversity.
Figure 2: A structural network for motility regulation.
Figure 3: Trypanosome ultrastructure.
Figure 4: Motility and immune evasion.

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Acknowledgements

Work in the authors' laboratories is supported by grants from The Royal Society, BBSRC and The Wellcome Trust. We gratefully thank K. Gull for his supportive advice and comments during preparation of this manuscript, and the anonymous reviewers for their constructive comments. We also thank colleagues who provided original images for Figs 1 and 3. M.L.G. is a Royal Society University Research Fellow. Work in the Gull laboratory in Oxford (N.P.) is supported by the Wellcome Trust.

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DATABASES

Entrez Genome Project

Chlamydomonas reinhardtii

Giardia lamblia

Tetrahymena thermophila

Toxoplasma gondii

Trypanosoma brucei

Paramecium tetraurelia

Plasmodium

OMIM

Alstrom

Bardet–Biedl

Meckel

FURTHER INFORMATION

Michael Ginger's homepage

Paul McKean's homepage

Glossary

Protists

Eukaryotes that cannot be classified as animals, fungi or plants. The kingdom Protista includes protozoa and algae.

Ciliates

A ubiquitous group of protists, members of which can be found in many wet environments. Ciliates are characterized by the hair-like covering of the cell body by hundreds of short cilia. Ciliary movement contributes to movement, cytokinesis and predation on other microbes.

Centriole

A barrel-shaped organelle that contains nine triplet-microtubules and that forms the basal body from which a flagellar axoneme is extended. In some eukaryotes, centrioles are required for mitosis. In Chlamydomonas reinhardtii, flagellar basal bodies are uncoupled from their associated axonemes to function as mitotic centrioles during division.

Apicomplexa

A phylum of obligate intracellular parasites that includes several important human pathogens, such as the malarial parasite Plasmodium falciparum, the opportunistic pathogen Toxoplasma gondii and the water-borne parasite Cryptosporidium hominis.

RNAi

A commonly used experimental tool to silence genes. In Trypanosoma brucei, RNAi is a very tractable reverse genetic approach for studying gene function. Less robust and often unstable RNAi systems are also available for motility studies in Chlamydomonas reinhardtii.

Reynolds number

A measure of the ratio of inertial forces to viscous forces that is used in fluid mechanics to quantify the relative importance of a type of force in a given flow condition.

Dyneins

Complex motor proteins that use the energy released from ATP hydrolysis to move towards the minus end of microtubules.

Diatoms

A major group of marine algae. Centric diatoms produce flagellate gametes.

Protozoa

Unicellular eukaryotes that do not possess the chitinous cell wall that is found in fungi. Protozoa are ubiquitous in aquatic and soil environments, where they make key ecological contributions. Several well-studied protozoa are parasites of medical, veterinary or agricultural significance.

Trypanosomatids

A family of flagellate parasites that includes monogenetic parasites of insects and digenetic parasites that are transmitted between mammalian or plant hosts by an invertebrate vector. Digenetic family members include the African sleeping sickness parasite Trypanosoma brucei, Chagas' disease parasite Trypanosoma cruzi and pathogenic Leishmania spp.

Procyclic trypomastigote

A morphological form of Trypanosoma brucei that migrates from the mid-gut of the tsetse fly vector. Like bloodstream trypanosomes, procyclic cells can be grown and genetically manipulated in culture. In both bloodstream and procyclic trypomastigotes, the flagellum emerges from the posterior end of the cell, is elongated in the direction of the anterior cell end and is attached along the length of the cell body.

Promastigote

Morphological form of Leishmania spp. that migrates through the digestive tract of the sandfly vector. A single free flagellum emerges from the anterior pole of the cell body in promastigotes.

Kinesins

Motor proteins that couple ATP hydrolysis to plus-end-directed movement along microtubules. In flagella, kinesins are required for intraflagellar transport and a kinesin-like protein is a component of the central pair microtubules.

IFT particles

Core components of the IFT machinery. Two large multisubunit IFT particle complexes have been characterized: complex A (classically associated with retrograde IFT) and complex B (associated with anterograde IFT). Each of these complexes contains its own unique set of widely-conserved protein subunits.

Amastigote

Pathogenic, immotile morphological forms of Leishmania spp. that replicate in acidic phagolysosomes of a host macrophage.

Kinetoplast

The mitochondrial genome in trypanosomatids. A kinetoplast consists of several thousand catenated circular DNA molecules, is replicated once per cell cycle and is attached to the flagellar basal body.

Chemical genetics

The use of small molecules, rather than genetic mutations, to interfere directly with protein function. In the case of trypanosome motility, small molecules could inhibit the activity of signalling enzymes, disrupt essential protein–protein interactions or be active against any of the 200 plus 'trypanosomatid specific' flagellum proteins that have been described.

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Ginger, M., Portman, N. & McKean, P. Swimming with protists: perception, motility and flagellum assembly. Nat Rev Microbiol 6, 838–850 (2008). https://doi.org/10.1038/nrmicro2009

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