The flagellum of Trypanosoma brucei: New tricks from an old dog

Abstract

African trypanosomes, i.e. Trypanosoma brucei and related sub-species, are devastating human and animal pathogens that cause significant human mortality and limit sustained economic development in sub-Saharan Africa. Trypanosoma brucei is a highly motile protozoan parasite and coordinated motility is central to both disease pathogenesis in the mammalian host and parasite development in the tsetse fly vector. Since motility is critical for parasite development and pathogenesis, understanding unique aspects of the T. brucei flagellum may uncover novel targets for therapeutic intervention in African sleeping sickness. Moreover, studies of conserved features of the T. brucei flagellum are directly relevant to understanding fundamental aspects of flagellum and cilium function in other eukaryotes, making T. brucei an important model system. The T. brucei flagellum contains a canonical 9 + 2 axoneme, together with additional features that are unique to kinetoplastids and a few closely-related organisms. Until recently, much of our knowledge of the structure and function of the trypanosome flagellum was based on analogy and inference from other organisms. There has been an explosion in functional studies in T. brucei in recent years, revealing conserved as well as novel and unexpected structural and functional features of the flagellum. Most notably, the flagellum has been found to be an essential organelle, with critical roles in parasite motility, morphogenesis, cell division and immune evasion. This review highlights recent discoveries on the T. brucei flagellum.

A coiled-coil- and C2-domain-containing protein is required for FAZ assembly and cell morphology in Trypanosoma brucei

“…The T. brucei flagellum and its attachment to the cell body are crucial for cell motility, cell division and cell morphogenesis (Ralston and Hill, 2008;Ralston et al, 2009;Vaughan, 2010). Although the exact mechanism of how flagellum assembly regulates cell morphology remains unclear, of particular interest is the function of the flagellum attachment zone (FAZ), a specialized cellular structure found in trypanosomatids (Sherwin and Gull, 1989a;Vickerman, 1962;Vickerman, 1969).…”

“…A single, membrane-bound flagellum plays crucial roles in cell motility, coordinated organelle segregation, cell division and morphogenesis (Ralston and Hill, 2008;Ralston et al, 2009;Vaughan, 2010). Normal function of the T. brucei flagellum relies on its attachment to the cell body through a flagellum attachment zone (FAZ).…”

ADF/cofilin-driven actin dynamics in early events ofLeishmaniacell division

“…Furthermore, it displays high nucleotide exchange but weak actin-filament-severing activities (Tammana et al, 2008). As the distributions of Cof and actin in Leishmania cells are largely polarized towards the flagellar pocket region where the basal body is located (Tammana et al, 2008), and as the cell division in trypanosomatids is initiated with basal body duplication followed by flagellum formation and flagellar pocket division (Ralston and Hill, 2008), we investigated the role of Cof-driven actin dynamics in Leishmania cell division. Results presented here indicate that actin dynamics has an important role in Leishmania cell division, especially in basal body separation and flagellar pocket division.…”

Membrane protein SMP-1 is required for normal flagellum function inLeishmania

“…Motile stages of these parasites produce a single flagellum that emerges from a specialized invagination in the plasma membrane, termed the flagellar pocket. The emergent flagellum contains a typical 9+2 microtubule axoneme that is supported by a paracrystalline structure called the paraflagellar rod (PFR) (Ginger et al, 2008;Ralston and Hill, 2008). The trypanosomatid flagellum and associated flagellar pocket is required for motility, endocytosis and exocytosis, and cytokinesis (Bonhivers et al, 2008;Broadhead et al, 2006;Ginger et al, 2008;Kohl et al, 2003;Ralston and Hill, 2008).…”

“…The emergent flagellum contains a typical 9+2 microtubule axoneme that is supported by a paracrystalline structure called the paraflagellar rod (PFR) (Ginger et al, 2008;Ralston and Hill, 2008). The trypanosomatid flagellum and associated flagellar pocket is required for motility, endocytosis and exocytosis, and cytokinesis (Bonhivers et al, 2008;Broadhead et al, 2006;Ginger et al, 2008;Kohl et al, 2003;Ralston and Hill, 2008). Specific nutrient transporters and signaling proteins are also targeted to the flagellar membrane, indicating a role for the flagellum in environmental sensing (Ginger et al, 2008;Oberholzer et al, 2007).…”