Intracellular Transport Systems in Trypanosomes : Function , Evolution , and Virulence

e surface of pathogenic trypanosomatids represents the host–parasite interface, and characterization of the surface molecules and their functions has yielded major insights into mechanisms of disease progression, immune modulation and immune evasion. Additionally, trypanosomatids place a particularly heavy emphasis onto use of the GPI anchor as a means for membrane attachment of proteins, glycoconjugates and glycolipids. Synthesis, degradation and maintenance of the surface are a function of the endomembrane system. Recent advances have begun to unravel the complexity of the trypanosome trafficking system, how it is regulated and the mechanisms that underpin protein sorting. Availability of complete genome data now allows molecular level comparisons between the TriTryps and their hosts, identifying unique aspects to trafficking pathways in trypansomes, as well as providing potential for more rational experimental manipulation of transport systems. ese aspects together with our current state of knowledge of the trypanosome trafficking system are discussed. Introduction and overview ! e characterization of the organelles and pathways followed by cargo proteins during exocytosis or endocytosis is an important area in eukaryotic cell biology (Palade, 1975; Helenius et al., 1983), especially in mammalian and yeast systems where major advances have been made in the analysis of transport steps at the molecular level. Amongst the biggest challenges remaining are determining how the different molecular assemblies and compartments are integrated to control the various transport steps. e principles coordinating the itinerary of lipids and proteins and the precise organization of each compartment are still poorly understood in any system (van Vliet et al., 2003). Both endocytosis and exocytosis are of significant interest in trypanosomatids as membrane trafficking is responsible for construction of the host—parasite interface, responses to the host immune system and expression of components required for cell invasion and adhesion (Figs. 9.1 and 9.2). Common to all trypanosomatids is the polarization of the majority of the membrane transport system—including the Golgi complex and endocytic system— to the posterior region of the cell, with all membrane exchange with the plasma membrane restricted to the flagellar pocket. e very distinct life cycles, surface molecules and mechanisms for immune evasion exploited by Leishmania, Trypanosoma cruzi Figure 9.1 Ultrastructure of the posterior part of bloodstream stage Trypanosoma brucei. The images show representative electron micrographs of non-dividing trypanosomes. (A) Overview of the intracellular membrane system between the flagellar pocket and the nuclear area. (B) Enlarged view of the flagellar pocket with budding clathrin-coated pits. (C) Early endosomes and recycling endosome can locate in close proximity to the single Golgi. (D) Detailed view of the Golgi apparatus and the ER exit site. (E) Recycling endosomes are flat and extended cisternae. For details see text. AC, acidocalcisome; BZ, budding zone; CCP, clathrin-coated pit; EE, early endosome; ER, endoplasmic reticulum; EXC, exocytic carrier; F, flagellum; FAZ, flagellar attachment zone; FP, flagellar pocket; G, Golgi apparatus; GL, glycosome; L, lysosome; LE, late endosome; MT-FAZ; microtubules of the flagellar attachment zone; PMT, pellicular microtubules; RE, recycling endosome; SC, surface coat; size bars: 1 μm (images: M. Morphew, J. R. McIntosh and M. Engstler). 282 | Engstler et al.