The diversity of Rab GTPases in Entamoeba histolytica

Saito‐Nakano, Yumiko; Loftus, Brendan J.; Hall, Neil; Nozaki, Tomoyoshi

doi:10.1016/j.exppara.2005.02.021

Cited by 108 publications

(111 citation statements)

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“…The significance of lineagespecific expansions in the Rab family has been previously acknowledged by phylogenetic analyses in various taxa (e.g. Lal et al, 2005;Rutherford and Moore, 2002;Saito-Nakano et al, 2005;Saito-Nakano et al, 2010). Our aim was not to provide a full description of all Rab duplication events that have occurred, but rather to reconstruct the Rab complement at important nodes of the eukaryotic phylogeny, and hence estimate the extent of innovation at the establishment of the major eukaryotic groups.…”

Section: Discussionmentioning

confidence: 99%

“…Systematic reconstructions deduced that the last eukaryotic common ancestor (LECA) possessed up to 14 ancient Rab paralogues, but only 8-10 of these were robustly reconstructed by phylogenetics (Bright et al, 2010;Pereira-Leal, 2008;Pereira-Leal and Seabra, 2001). Most unicellular eukaryotes possess approximately 10-20 distinct Rabs, but several have many more (Bright et al, 2010;Carlton et al, 2007;Saito-Nakano et al, 2005), whereas multicellular organisms can possess over 60 (Pereira-Leal and Seabra, 2001;Rutherford and Moore, 2002). The precise biological implications of an increased Rab repertoire remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Sculpting the endomembrane system in deep time: High resolution phylogenetics of Rab GTPases

Eliáš

Brighouse

Gabernet-Castello

et al. 2012

Journal of Cell Science

149

257

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SummaryThe presence of a nucleus and other membrane-bounded intracellular compartments is the defining feature of eukaryotic cells. Endosymbiosis accounts for the origins of mitochondria and plastids, but the evolutionary ancestry of the remaining cellular compartments is incompletely documented. Resolving the evolutionary history of organelle-identity encoding proteins within the endomembrane system is a necessity for unravelling the origins and diversification of the endogenously derived organelles. Comparative genomics reveals events after the last eukaryotic common ancestor (LECA), but resolution of events prior to LECA, and a full account of the intracellular compartments present in LECA, has proved elusive. We have devised and exploited a new phylogenetic strategy to reconstruct the history of the Rab GTPases, a key family of endomembrane-specificity proteins. Strikingly, we infer a remarkably sophisticated organellar composition for LECA, which we predict possessed as many as 23 Rab GTPases. This repertoire is significantly greater than that present in many modern organisms and unexpectedly indicates a major role for secondary loss in the evolutionary diversification of the endomembrane system. We have identified two Rab paralogues of unknown function but wide distribution, and thus presumably ancient nature; RabTitan and RTW. Furthermore, we show that many Rab paralogues emerged relatively suddenly during early metazoan evolution, which is in stark contrast to the lack of significant Rab family expansions at the onset of most other major eukaryotic groups. Finally, we reconstruct higher-order ancestral clades of Rabs primarily linked with endocytic and exocytic process, suggesting the presence of primordial Rabs associated with the establishment of those pathways and giving the deepest glimpse to date into pre-LECA history of the endomembrane system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sculpting the endomembrane system in deep time: High resolution phylogenetics of Rab GTPases

Eliáš

Brighouse

Gabernet-Castello

et al. 2012

Journal of Cell Science

149

257

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“…It has also been shown that AP-1 together with Rab4 is involved in the regulation of the vesicle formation from endosomes (Pagano et al, 2004). Our genome-wide survey of E. histolytica revealed that this organism possesses large, intermediate, and small subunits of AP complex and clathrin heavy chain, but lacks Rab4, Rab9 (Saito-Nakano et al, 2005), TIP47 (unpublished results), and CI-MPR (see above). It is conceivable that the amebic retromerlike complex regulates the retrieval of not-yet-identified hydrolase receptor(s) in a coordinated interaction with other Rab and adaptor proteins.…”

Section: Colocalization Of Ehrab7a and Ehvps26 By Immunofluorescence mentioning

confidence: 99%

“…E. histolytica reveals only two developmental stages, dividing trophozoite and dormant cyst stage, in its simplified life cycle (Ravdin, 1988). Despite being unicellular throughout its life cycle, this protist shows remarkable complexity of Rab proteins; it possesses more than 90 Rab genes in the genome, highlighting E. histolytica as an organism with extremely diverse and complex Rab functions Saito-Nakano et al, 2005). Vesicular trafficking plays an This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-04 -0283) on August 24, 2005. indispensable role for this organisms in nutrient uptake by ingestion and degradation of microorganisms in the large intestine, and also in secretion of cyto-and histolytic degradative proteins including cysteine proteases (CP; Que and Reed, 2000) and pore forming peptides (amoebapore: AP; Zhang et al, 2004), both of which have been implicated for colonization in mammalian tissues and evasion from host immune system.…”

Section: Introductionmentioning

confidence: 99%

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

Nakada‐Tsukui

Saito‐Nakano

Ali

et al. 2005

MBoC

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137

173

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Vesicular trafficking plays an important role in a virulence mechanism of the enteric protozoan parasite Entamoeba histolytica as secreted and lysosomal cysteine protease (CP) contributes to both cytolysis of tissues and degradation of internalized host cells. Despite the primary importance of intracellular sorting in pathogenesis, the molecular mechanism of CP trafficking remains largely unknown. In this report we demonstrate that transport of CP is regulated through a specific interaction of Rab7A small GTPase (EhRab7A) with the retromerlike complex. The amoebic retromerlike complex composed of Vps26, Vps29, and Vps35 was identified as EhRab7A-binding proteins. The amoebic retromerlike complex specifically bound to GTP-EhRab7A, but not GDP-EhRab7A through the direct binding via the carboxy terminus of EhVps26. In erythrophagocytosis the retromerlike complex was recruited to prephagosomal vacuoles, the unique preparatory vacuole of digestive enzymes, and later to phagosomes. This dynamism was indistinguishable from that of EhRab7A, and consistent with the premise that the retromerlike complex is involved in the retrograde transport of putative hydrolase receptor(s) from preparatory vacuoles and phagosomes to the Golgi apparatus. EhRab7A overexpression caused enlargement of lysosomes and decrease of the cellular CP activity. The reduced CP activity was restored by the coexpression of EhVps26, implying that the EhRab7A-mediated transport of CP to phagosomes is regulated by the retromerlike complex. INTRODUCTIONRab GTPases play an essential role to regulate intracellular membrane trafficking. The compartmentalization and functions of Rab proteins are modulated at multiple layers of mechanisms including isoprenylation of the carboxy terminus, nucleotide exchange, and binding of specific effector molecules (Stenmark and Olkkonen, 2001;Takai et al., 2001;Tuvim et al., 2001). Among these modulators, effectors play key roles in the control of 7-90 Rab proteins depending on organisms from fission yeast and amoeba to mammals and plants. A variety of effectors have been identified and shown to interact with specific Rab protein. For instance, regulatory secretions of neurotransmitters from neurons or insulin from pancreatic ␤-cells are regulated by the specific interaction of Rab3 with its effectors (Jahn and Sudhof, 1999). At least four proteins, Rabphilin3, Rim1, Rim2, and Noc2, are known to bind Rab3 and recruit cAMP-GEFII, 14 -3-3, and zyxin, respectively, to regulate cAMP responsiveness, phosphoserine-dependent signaling, and the interaction with cytoskeleton (Kotake et al., 1997;Ozaki et al., 2000;Sun et al., 2003). The specificity of the Rab-effector interaction is attributable to primary sequence motifs in only a few cases including exophilins or Slip/Slac2, Rab3, and Rab27 effectors (Izumi et al., 2003). However, the majority of Rab effectors lack recognizable conserved binding motifs. For instance, Rab5 effectors, rabaptin-5, Rabex-5, EEA1, Rabenosyn-5, hVps34/p150, p110␤/p35␣, rabip4Ј, and rabankyrin-5, which a...

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“…Other eukaryotes have fewer Rab proteins; Caenorhabditis elegans has 29 family members, Drosophila melanogaster has 26 members, and the yeast Saccharomyces cerevisiae has 11 members. As a model system, the 11 Rab proteins of the single-celled eukaryotic microbe S. cerevisiae can be considered the most minimal "membrome" (24), as other single-celled eukaryotes utilized as model systems contain a numerically larger set of Rab-encoding genes (35,49). A distinctive feature of the Rab protein is its steady-state localization to the cytosolic surface of a particular endomembrane.…”

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confidence: 99%

Bioinformatic and Comparative Localization of Rab Proteins Reveals Functional Insights into the Uncharacterized GTPases Ypt10p and Ypt11p

Frei

Rahl

Nussbaum

et al. 2006

Molecular and Cellular Biology

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A striking characteristic of a Rab protein is its steady-state localization to the cytosolic surface of a particular subcellular membrane. In this study, we have undertaken a combined bioinformatic and experimental approach to examine the evolutionary conservation of Rab protein localization. A comprehensive primary sequence classification shows that 10 out of the 11 Rab proteins identified in the yeast (Saccharomyces cerevisiae) genome can be grouped within a major subclass, each comprising multiple Rab orthologs from diverse species. We compared the locations of individual yeast Rab proteins with their localizations following ectopic expression in mammalian cells. Our results suggest that green fluorescent protein-tagged Rab proteins maintain localizations across large evolutionary distances and that the major known player in the Rab localization pathway, mammalian Rab-GDI, is able to function in yeast. These findings enable us to provide insight into novel gene functions and classify the uncharacterized Rab proteins Ypt10p (YBR264C) as being involved in endocytic function and Ypt11p (YNL304W) as being localized to the endoplasmic reticulum, where we demonstrate it is required for organelle inheritance.All eukaryotic cells are compartmentalized into distinct membrane-bound organelles and require tightly regulated transport of proteins and lipids between these compartments. Members of the Rab family of small GTPases are major regulators of protein and lipid traffic in the secretory and endocytic pathways (46,65). The action of Rab proteins in membrane transport was discovered with the identification of the SEC4 and YPT1 genes in yeast (Saccharomyces cerevisiae) (51, 52) and related proteins, termed Rab proteins, from mammals (10). Rab proteins comprise the most numerous subfamily of the Ras superfamily, and many are functionally uncharacterized. It is not clear whether Rab proteins regulate events that take place in the donor compartment, the vesicle or transport carrier, the acceptor compartment, or multiple locations. Also not known is whether a function(s) can be described for Rab proteins in general or whether this must be considered on a case-by-case basis. However, it is clear that Rab proteins are essential for eukaryotic cells and absolutely required for the function of all organelles connected by SNARE-mediated membrane traffic.With the completion of eukaryotic genome sequencing projects, there have been efforts to catalog the numbers of GTPase superfamily proteins. Membrane traffic in higher eukaryotes connects multiple compartments, and one reflection of this complexity may be the finding that humans have at least 60 different Rab family members (24,55,57). Other eukaryotes have fewer Rab proteins; Caenorhabditis elegans has 29 family members, Drosophila melanogaster has 26 members, and the yeast Saccharomyces cerevisiae has 11 members. As a model system, the 11 Rab proteins of the single-celled eukaryotic microbe S. cerevisiae can be considered the most minimal "membrome" (24), as other single-celle...

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The diversity of Rab GTPases in Entamoeba histolytica

Cited by 108 publications

References 26 publications

Sculpting the endomembrane system in deep time: High resolution phylogenetics of Rab GTPases

Sculpting the endomembrane system in deep time: High resolution phylogenetics of Rab GTPases

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

Bioinformatic and Comparative Localization of Rab Proteins Reveals Functional Insights into the Uncharacterized GTPases Ypt10p and Ypt11p

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