Intracellular Trafficking in the Trypanosomatids

Abstract

Trypanosomes are members of the kinetoplastida, a group of divergent protozoan parasites responsible for considerable morbidity and mortality worldwide. These organisms have highly complex life cycles requiring modification of their cell surface together with engagement of immune evasion systems to effect survival; both processes intimately involve the membrane trafficking system. The completion of three trypanosomatid and several additional protist genomes in the last few years is providing an exciting opportunity to evaluate, at the molecular level, the evolution and diversity of membrane trafficking across deep evolutionary time as well as to analyse in unprecedented detail the membrane trafficking systems of trypanosomes.

Life and times: synthesis, trafficking, and evolution of VSG

“…indicate that the major coding variance resides within those genes encoding surface determinants, with a remarkable level of conservation for most other gene functional classes, even extending to the level of retaining synteny and polycistronic transcription unit composition [85]. This insight agrees well with much of the earlier biochemical analysis demonstrating clear diversification of the surface composition of the African and American trypanosomes and Leishmania spp, and is presumably a reflection of the major emphasis of selective pressure for parasites with radically different life cycles and styles [86].…”

“…The massive dominance of the trypanosome surface by VSG implied that mechanisms for protein transport, targeting, and sorting may be distinct from mammalian cells, where most surface molecules have a trans -membrane domain, but it is now clear that many other trypanosomatids also rely heavily on a GPI anchor for surface molecule anchoring, suggesting broader significance for observations in Trypanosoma brucei [16]. In this review, we consider the molecular mechanisms that participate in the synthesis, targeting, and turnover of VSG, how these differ from canonical views of protein trafficking and modifications, and what such modifications may mean, both for VSG itself and for the trypanosome more generally, with some speculations on how the system arose.…”

Evolutionary reconstruction of the retromer complex and its function in Trypanosoma brucei

“…T. brucei Vps5 is strongly upregulated in the mammalian infective form, compared with its expression in the insect proliferative stage, and thus could be important for pathogenesis (Koumandou et al, 2008). Indeed, qRT-PCR analysis confirmed that all components of retromer identified by comparative genomics in T. brucei are upregulated in the mammalian form; this might be related to the more active lysosomal delivery route in the procyclic stage, whereas in the bloodstream stage recycling is the major trafficking route in terms of flux (Field et al, 2007b). Retromer might contribute here, rescuing proteins before lysosomal delivery.…”

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

“…Several studies have shown that the flagellar-pocket membrane is biochemically distinct from the flagellum or pellicular membrane and is central for trafficking of various GPI-anchored proteins (Schwartz et al, 2005). These trafficking events involve recycling of several important proteins, such as clathrin, GTPase and Rab proteins (Garcia-Salcedo et al, 2004;Field et al, 2007), maintaining the flagellar-pocket membrane in a highly dynamic state. Since the flagellar-pocket membrane is devoid of microtubule cytoskeleton, it is possible that actin, as the flagellar-pocket cytoskeleton, regulates various dynamic activities of this organelle, such as endocytosis and membranefurrow formation, during cell division.…”