Key Points
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Trypanosomes are flagellated single cell pathogens that are responsible for several diseases. The African trypanosome causes sleeping sickness, a disease leading to fatal coma and organ failure if untreated.
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Trypanosomes possess a specialized plasma membrane invagination, the flagellar pocket, where the flagellum emerges from the cytoplasm. The organelle is essential for viability and central to cellular structure and function, with roles encompassing trafficking, organelle positioning and cytoskeletal coordination.
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The surface of the African trypanosome is dominated by the glycosylphosphatidylinositol-anchored variant surface glycoprotein (VSGs), which is the primary mechanism of immune evasion through antigenic variation. Extremely rapid endocytosis is associated with both mammalian infectivity and expression of VSGs.
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The protein composition of the flagellar pocket is distinct from the bulk plasma membrane, and restriction of invariant receptors in the structure is thought to contribute to evading the host immune system.
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All macromolecular exchange with the trypanosome endomembrane system and the environment is mediated through the flagellar pocket. A rapid recycling system, which begins and ends at the pocket membrane, is responsible for removing surface-bound immune effectors while maintaining homeostasis at the surface.
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The flagellar pocket is physically connected to the flagellum, basal body and probably additional organelles; it is apparent that the pocket is essential for faithful positioning of multiple structures during cytokinesis.
Abstract
Trypanosomes are important disease agents and excellent models for the study of evolutionary cell biology. The trypanosome flagellar pocket is a small invagination of the plasma membrane where the flagellum exits the cytoplasm and participates in many cellular processes. It is the only site of exocytosis and endocytosis and part of a multiorganelle complex that is involved in cell polarity and cell division. Several flagellar pocket-associated proteins have been identified and found to contribute to trafficking and virulence. In this Review we discuss the contribution of the flagellar pocket to protein trafficking, immune evasion and other processes.
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Work in the authors' laboratories is supported mainly by the Wellcome Trust, which is gratefully acknowledged.
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Glossary
- Flagellum
-
A tail-like structure emerging from the cell. In trypanosomes the flagellum consists of a 9+2 microtubule configuration axoneme and a paraflagellar rod. The whole structure is attached to the cell body and anchored through connections to the flagellar attachment zone, a specialization of a subset of microtubules subtending the plasma membrane.
- Basal body
-
An organelle that is formed from the centriole and, in the case of many flagellates, that acts as the base of the flagellum from which the axoneme is built. There are two basal bodies per cell, only one of which gives rise to a flagellum. Duplication of basal bodies is a key step in early mitosis.
- Variant surface glycoprotein
-
(VSG). A ∼60kDa glycosylphosphatidylinositol-anchored glycoprotein that is expressed on the surface of African trypanosomes at extreme density. By sequentially expressing distinct VSG genes, trypanosomes achieve antigenic variation.
- Facile vaccination
-
Vaccination against bacterial infections using heat killed bacteria or surface proteins, which can be regarded as facile (that is, easy), at least conceptually. Such approaches have not been successful against many protozoan parasites.
- Subpellicular array
-
A regularly spaced microtubule array that is located just beneath the plasma membrane in trypanosomes and is responsible for maintaining the shape of the cell.
- Axoneme
-
The inner core of the flagellum and cilia in eukaryotes. Most possess nine outer ring microtubule doublets and an inner central pair of microtubules.
- Orthologue
-
Homologous sequences that are separated only by a speciation event. If genes are orthologous they share common ancestry, and this allows inference of similar function when comparing two distinct lineages.
- Acidocalcisome
-
An electron-dense acidic membrane-bound cytoplasmic organelle containing a matrix of pyrophosphate and polyphosphates with bound calcium and additional cations. Acidocalcisomes are found in a wide range of eukaryotes and prokaryotes.
- Clathrin-coated bouton
-
(from the French for button). A small bud or button-like structure that extends from the central region of the sorting endosome and where clathrin is preferentially localized. It is thought that the differential morphology and protein composition allows the structure to selectively sort proteins.
- Paracrystalline inclusion
-
An inclusion in membrane-bound structures found in the lumen of the flagellar pocket that have small lattice-like structures separated by regions of less clear order. Such structures frequently arise by high concentrations of proteins accumulating and forming partially ordered aggregates.
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Field, M., Carrington, M. The trypanosome flagellar pocket. Nat Rev Microbiol 7, 775–786 (2009). https://doi.org/10.1038/nrmicro2221
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DOI: https://doi.org/10.1038/nrmicro2221
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