The Ancient Small GTPase Rab21 Functions in Intermediate Endocytic Steps in Trypanosomes

Ali, Moazzam; Leung, Ka Fai; Field, Mark C.

doi:10.1128/ec.00269-13

Cited by 21 publications

(20 citation statements)

References 73 publications

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“…The swollen posterior vacuoles seen in the ␣-KDE1 RNAi T. brucei cells (Fig. 1C and 2B and C) resembled the swollen flagellar pocket in BF T. brucei following RNAi silencing of genes encoding proteins involved in endocytosis (22)(23)(24)(25)(26). However, we observed no change in endocytosis rates of ConA (see Fig.…”

Section: Resultsmentioning

confidence: 62%

The Krebs Cycle Enzyme α-Ketoglutarate Decarboxylase Is an Essential Glycosomal Protein in Bloodstream African Trypanosomes

2015

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␣-Ketoglutarate decarboxylase (␣-KDE1) is a Krebs cycle enzyme found in the mitochondrion of the procyclic form (PF) of Trypanosoma brucei. The bloodstream form (BF) of T. brucei lacks a functional Krebs cycle and relies exclusively on glycolysis for ATP production. Despite the lack of a functional Krebs cycle, ␣-KDE1 was expressed in BF T. brucei and RNA interference knockdown of ␣-KDE1 mRNA resulted in rapid growth arrest and killing. Cell death was preceded by progressive swelling of the flagellar pocket as a consequence of recruitment of both flagellar and plasma membranes into the pocket. BF T. brucei expressing an epitope-tagged copy of ␣-KDE1 showed localization to glycosomes and not the mitochondrion. We used a cell line transfected with a reporter construct containing the N-terminal sequence of ␣-KDE1 fused to green fluorescent protein to examine the requirements for glycosome targeting. We found that the N-terminal 18 amino acids of ␣-KDE1 contain overlapping mitochondrion-and peroxisome-targeting sequences and are sufficient to direct localization to the glycosome in BF T. brucei. These results suggest that ␣-KDE1 has a novel moonlighting function outside the mitochondrion in BF T. brucei.

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Section: Resultsmentioning

confidence: 62%

The Krebs Cycle Enzyme α-Ketoglutarate Decarboxylase Is an Essential Glycosomal Protein in Bloodstream African Trypanosomes

2015

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“…This is also supported by the presence of clathrin buds on endosomal structures that appear to exclude VSG, suggesting that recognition of trans-membrane domain proteins may take place at internal compartments and possibly would be mediated by AP-1 [8,27,28]. Subsequently, the endocytic process involves transitioning through additional compartments defined by Rab21, Rab28 and finally Rab7 [29][30][31]. Quite what the specific functions of these steps are remains to be elucidated but control does appear to be mediated by the vacuolar protein sorting 9 (Vps9), a process conserved with mammalian cells [32].…”

Section: A Dynamic Surface For Host and Environmental Interactionsmentioning

confidence: 82%

Adaptation and Therapeutic Exploitation of the Plasma Membrane of African Trypanosomes

Quintana¹,

Pino²,

Yamada³

et al. 2018

Preprint

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African trypanosomes are an early branch in eukaryotic evolution and developed a unique endomembrane system as an adaptation to their parasitic life style. The key virulence mechanism of many pathogens is successful immune evasion to enable survival within the host, which is a feature requiring both genetic events and membrane transport in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unravelled some of the connections between these processes and highlighted how immune evasion mechanisms associated with adaptations in membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purpose.

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“…1 and data not shown). What is so fundamentally different between cells of the different angiosperms that this Rab paralog, and presumably a specific cellular process regulated by Rab21 (most likely in the endocytic pathway [54]), could have been lost from the A. thaliana lineage? An even more extreme case is represented by the pair of organisms nominally representing the same species, M. pusilla CCMP1545 and M. pusilla NOUM17 (sometimes referred to as Micromonas sp.…”

Section: Cell Biological Implications Of the Varying Rab Complement Imentioning

confidence: 99%

Contrasting patterns in the evolution of the Rab GTPase family in Archaeplastida

Petrželková

Eliáš

2014

Acta Soc Bot Pol

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Rab GTPases are a vast group of proteins serving a role of master regulators in membrane trafficking in eukaryotes. Previous studies delineated some 23 Rab and Rab-like paralogs ancestral for eukaryotes and mapped their current phylogenetic distribution, but the analyses relied on a limited sampling of the eukaryotic diversity. Taking advantage of the recent growth of genome and transcriptome resources for phylogenetically diverse plants and algae, we reanalyzed the evolution of the Rab family in eukaryotes with the primary plastid, collectively constituting the presumably monophyletic supergroup Archaeplastida. Our most important novel findings are as follows: (i) the ancestral set of Rabs in Archaeplastida included not only the paralogs Rab1, Rab2, Rab5, Rab6, Rab7, Rab8, Rab11, Rab18, Rab23, Rab24, Rab28, IFT27, and RTW (=Rabl2), as suggested previously, but also Rab14 and Rab34, because Rab14 exists in glaucophytes and Rab34 is present in glaucophytes and some green algae; (ii) except in embryophytes, Rab gene duplications have been rare in Archaeplastida. Most notable is the independent emergence of divergent, possibly functionally novel, in-paralogs of Rab1 and Rab11 in several archaeplastidial lineages; (iii) recurrent gene losses have been a significant factor shaping Rab gene complements in archaeplastidial species; for example, the Rab21 paralog was lost at least six times independently within Archaeplastida, once in the lineage leading to the "core" eudicots; (iv) while the glaucophyte Cyanophora paradoxa has retained the highest number of ancestral Rab paralogs among all archaeplastidial species studied so far, rhodophytes underwent an extreme reduction of the Rab gene set along their stem lineage, resulting in only six paralogs (Rab1, Rab2, Rab6, Rab7, Rab11, and Rab18) present in modern red algae. Especially notable is the absence of Rab5, a virtually universal paralog essential for the endocytic pathway, suggesting that endocytosis has been highly reduced or rewired in rhodophytes.

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The Ancient Small GTPase Rab21 Functions in Intermediate Endocytic Steps in Trypanosomes

Cited by 21 publications

References 73 publications

The Krebs Cycle Enzyme α-Ketoglutarate Decarboxylase Is an Essential Glycosomal Protein in Bloodstream African Trypanosomes

The Krebs Cycle Enzyme α-Ketoglutarate Decarboxylase Is an Essential Glycosomal Protein in Bloodstream African Trypanosomes

Adaptation and Therapeutic Exploitation of the Plasma Membrane of African Trypanosomes

Contrasting patterns in the evolution of the Rab GTPase family in Archaeplastida

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