Flagellar membrane trafficking in kinetoplastids

Abstract

Trypanosomes are flagellated protozoa belonging to the order Kinetoplastidae. Three trypanosomes, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania are the causative agents of the human diseases: African sleeping sickness, Chagas disease, and leishmaniasis, respectively. These organisms have complex life cycles involving bloodsucking insects and vertebrates; humans become infected when infested insects feed on them. The trypanosome contains several unique organelles, one of the most important and conspicuous of which is the flagellum (Fig. 1). The trypanosome flagellum is a unique multifunctional organelle that plays critical roles in motility, chemotaxis, cell signaling, and host cell invasion (Landfear and Ignatushchenko 2001; Gull 2003; Hill 2003). In addition to containing a classical axonemal microtubular motor, the trypanosome flagellum also includes a paracrystalline structure called the paraflagellar rod (PFR), positioned alongside the axoneme. The flagellum emerges from the cell body from an invagination known as the flagellar pocket. As the cell body is constrained by a tight corset of cross-linked subpellicular microtubules (Fig. 1b), all vesicular trafficking into and out of the cell occurs at the non-microtubule-bound flagellar pocket, as does the trafficking of flagellar membrane-associated proteins between the cytoplasm and the flagellum (Bloodgood 1990; McConville et al. 2002). Because no new protein synthesis takes place in the flagellum, all protein components must be imported to the flagellum from the cell body, also via the flagellar pocket. To enter the flagellum, a protein must first pass through a cytoskeletal “neck” region within the flagellar pocket known as the flagellar pore complex (Rosenbaum and Witman 2002; Gull 2003). This complex, which contains structures including the basal body and transition zone filaments, is believed to act as a “stopper” for the flagellum, providing a selective barrier for protein entry (Vickerman and Preston 1976; Dentler and Adams 1992). Regulated flagellar protein import creates a flagellar microenvironment that is unique from that of the rest of the organism, where some of the protein and lipid components differ in composition from those in the cell body (Bloodgood 1990; Landfear and Ignatushchenko 2001). Because of differences in composition and function, the surface membrane of a trypanosome is divided into three distinct but contiguous domains: the pellicular (cell body) membrane, flagellar membrane, and flagellar pocket membrane (Balber 1990; Landfear and Ignatushchenko 2001; Gull 2003). As the flagellum is not a “closed” membrane-bound organelle like the mitochondrion or a lysosome, it has this far Parasitol Res DOI 10.1007/s00436-006-0329-2