Dileucine signal-dependent and AP-1-independent targeting of a lysosomal glycoprotein in Trypanosoma brucei

Allen, Clare L.; Liao, Dangjin; Chung, Wei-Lian; Field, Mark C.

doi:10.1016/j.molbiopara.2007.07.020

Cited by 32 publications

(44 citation statements)

References 41 publications

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“…Furthermore, we infrequently detected structures with a high proportion of intralumenal vesicles (Fig. 7E), as previously been reported when AP-1 was silenced in trypanosomes, which might correspond to multivesicular bodies or other stress-induced structures (Allen et al, 2007). We also observed the appearance of highly vesiculated structures in close proximity to the flagellar pocket; these structures might represent residual material derived from the Golgi complex, post-Golgi transport intermediates and/or endosomal structures (Fig.…”

Section: Golgi Complex Ultrastructure Is Perturbed By T Brucei Rab28supporting

confidence: 86%

Rab28 function in trypanosomes: interactions with retromer and ESCRT pathways

Lumb

Leung

DuBois

et al. 2011

Journal of Cell Science

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SummaryEarly endosomal cargo is typically targeted to either a degradative or recycling pathway. Despite established functions for the retromer and ESCRT complexes at late endosomes/multivesicular bodies, the mechanisms integrating and coordinating these functions remain largely unknown. Rab family GTPases are key membrane trafficking organizers and could contribute. Here, in the unicellular organism Trypanosoma brucei, we demonstrate that Rab28 locates to the endosomal pathway and partially colocalizes with Vps23, an ESCRT I component. Rab28 is required for turnover of endocytosed proteins and for lysosomal delivery of protein cargo. Using RNA interference we find that in Rab28-depleted cells, protein levels of ESCRT I (Vps23/28) and retromer (Vps26) are also decreased, suggesting that Rab28 is an important regulator of these factors. We suggest that Rab28 coordinates the activity of retromer-dependent trafficking and ESCRT-mediated degradative pathways.

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Section: Golgi Complex Ultrastructure Is Perturbed By T Brucei Rab28supporting

confidence: 86%

Rab28 function in trypanosomes: interactions with retromer and ESCRT pathways

Lumb

Leung

DuBois

et al. 2011

Journal of Cell Science

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“…RNA interference knockdown of AP-1 subunits leads to pleiotropic effects in endosomal membrane traffic and cell division, although protein transport to the lysosome is apparently not affected (1,44). In contrast, genetic deletion of AP-1 1 or 1 subunits in Leishmania mexicana mexicana has little effect on the growth of promastigote stages in rich medium (19).…”

mentioning

confidence: 98%

“…Recent studies have shown that AP-1 is essential for the growth of the major developmental stages of Trypanosoma brucei (1). RNA interference knockdown of AP-1 subunits leads to pleiotropic effects in endosomal membrane traffic and cell division, although protein transport to the lysosome is apparently not affected (1,44).…”

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confidence: 99%

Leishmania Adaptor Protein-1 Subunits Are Required for Normal Lysosome Traffic, Flagellum Biogenesis, Lipid Homeostasis, and Adaptation to Temperatures Encountered in the Mammalian Host

Vince¹,

Tull²,

Spurck

et al. 2008

Eukaryot Cell

103

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The adaptor protein-1 (AP-1) complex is involved in membrane transport between the Golgi apparatus and endosomes. In the protozoan parasite Leishmania mexicana mexicana, the AP-1 1 and 1 subunits are not required for growth at 27°C but are essential for infectivity in the mammalian host. In this study, we have investigated the function of these AP-1 subunits in order to understand the molecular basis for this loss of virulence. The 1 and 1 subunits were localized to late Golgi and endosome membranes of the major parasite stages. Parasite mutants lacking either AP-1 subunit lacked obvious defects in Golgi structure, endocytosis, or exocytic transport. However, these mutants displayed reduced rates of endosome-to-lysosome transport and accumulated fragmented, sterol-rich lysosomes. Defects in flagellum biogenesis were also evident in nondividing promastigote stages, and this phenotype was exacerbated by inhibitors of sterol and sphingolipid biosynthesis. Furthermore, both AP-1 mutants were hypersensitive to elevated temperature and perturbations in membrane lipid composition. The pleiotropic requirements for AP-1 in membrane trafficking and temperature stress responses explain the loss of virulence of these mutants in the mammalian host.

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“…In this group of flagellate protozoa, the trafficking system has been previously characterized . Trypanosomes contain glycosil-phosphatidylinositol-anchored proteins and morphologically-related MVB structures, and also exhibit ubiquitin-dependent internalization of transmembrane proteins for degradation (Allen et al, 2007;Chung et al, 2004). The functional conservation of the ESCRT system has been confirmed in Trypanosome brucei.…”

Section: Endocytosis and The Mvb Pathway In Parasitic Protozoamentioning

confidence: 97%

“…Among the latter is the ability of eukaryotic cells to incorporate macromolecules, complexes and other cells through endocytosis (de Souza et al, 2009 (Allen et al, 2007;Tse et al, 2004;Yang et al, 2004). Lysosomal targeting of ubiquitinated cargo by ESCRT complexes is conserved in animals and fungi (Leung et al, 2008).…”

Section: Evolution Of the Escrt Machinerymentioning

confidence: 99%