Human Orthologs of Yeast Vacuolar Protein Sorting Proteins Vps26, 29, and 35: Assembly into Multimeric Complexes

Haft, Carol Renfrew; Sierra, Maria de la Luz; Bafford, Richard A.; Lesniak, Maxine A.; Barr, Valarie A.; Taylor, Simeon I.

doi:10.1091/mbc.11.12.4105

Cited by 284 publications

(308 citation statements)

References 24 publications

(42 reference statements)

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“…We verified a direct interaction between the amino-terminal three fourths (a.a. 1-295) of EhVps26 (EhVps26⌬C) and the aminoterminal third (a.a. 1-305) of EhVps35 (EhVps35N) and between the carboxyl-terminal fourth (a.a. 583-757) of EhVps35 (EhVps35C) and EhVps29, as well as lack of interaction between EhVps26 and EhVps29 by yeast two-hybrid system (unpublished data). These interactions are similar to those found for the mammalian retromer complex (Haft et al, 2000). On the other hand, we failed to detect the binding between EhRab7A (neither wild-type nor GTP-locked form) and EhVps26 (full-length, amino-, or carboxyl-terminus; unpublished data), which indicates that the interaction is transient and weak in this assay system.…”

Section: Molecular Biology Of the Cell 5298supporting

confidence: 86%

“…Because of the lack of these two components, the E. histolytica retromerlike complex likely plays a different role. Size fractionation by gel filtration revealed that the amoebic retromerlike complex showed an apparent molecular weight of 300 -500 kDa (unpublished data), which is comparable to that in mammalian cells (Haft et al, 2000). The missing components, sorting nexins and Vps5/17, possess PX domain and BAR domain for the interaction with phosphatidyl inositol 3-phosphate and the curbed membrane (Seaman and Williams, 2002;Habermann, 2004;Seaman, 2005).…”

Section: Identification Of a Retromerlike Complex As A Novel Ehrab7a mentioning

confidence: 84%

“…The retromer complex is composed of four or five components: Vps5p, Vps17p, Vps26p, Vps29p, and Vps35p in yeast (Reddy and Seaman, 2001) and Vps5p-homologue sorting nexin1 (SNX1), Vps26, Vps29, and Vps35 in mammals (Haft et al, 2000). However, only Vps26, Vps29, and Vps35, but not Vps5, SNX1, or Vps17, are present in the genome database of E. histolytica .…”

Section: Identification Of a Retromerlike Complex As A Novel Ehrab7a mentioning

confidence: 99%

“…The top and bottom bands were unequivocally assigned to the amoebic homologue of Vps35p and Vps26p, respectively, as 43 of 113 peptides derived from the top band and 27 of 78 peptides from the bottom band showed identity to the amoebic Vps35 and Vps26 homologues, respectively (39 -51% coverage; unpublished data). Vps26 and Vps35 are known as components of retromer complex and are implicated for the retrograde transport of the hydrolase receptor from the late endosomes to the transGolgi apparatus (Seaman, 2005).The retromer complex is composed of four or five components: Vps5p, Vps17p, Vps26p, Vps29p, and Vps35p in yeast (Reddy and Seaman, 2001) and Vps5p-homologue sorting nexin1 (SNX1), Vps26, Vps29, and Vps35 in mammals (Haft et al, 2000). However, only Vps26, Vps29, and Vps35, but not Vps5, SNX1, or Vps17, are present in the genome database of E. histolytica .…”

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confidence: 99%

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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

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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Section: Molecular Biology Of the Cell 5298supporting

confidence: 86%

Section: Identification Of a Retromerlike Complex As A Novel Ehrab7a mentioning

confidence: 84%

Section: Identification Of a Retromerlike Complex As A Novel Ehrab7a mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

137

173

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“…Since then, retromer has been implicated in a broad range of protein-sorting pathways and has most recently been shown to be required for the maintenance of proper Wnt secretion in the development of both Caenorhabditis elegans and Drosophila melanogaster (Belenkaya et al, 2008;Franch-Marro et al, 2008;Pan et al, 2008;Port et al, 2008;Yang et al, 2008), underscoring its importance in retrograde transport. In yeast retromer is composed of five proteins that assemble into two subcomplexes: Vps5 and Vps17 (Snx1/ Snx2 and Snx5/Snx6 in mammals) and Vps26, Vps29, and Vps35 (and the homologous proteins in metazoans; Seaman et al, 1998;Haft et al, 2000;Wassmer et al, 2007). Vps5 and Vps17 are members of the sorting nexin family of proteins and are responsible for localizing the retromer complex to tubular endosomal membranes via the concerted action of their BAR (Bin/Amphiphysin/RVS) and PX (phox homology) domains (Carlton et al, 2004;Seet and Hong, 2006).…”

Section: Introductionmentioning

confidence: 99%

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Strochlic

Schmiedekamp

Lee

et al. 2008

MBoC

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Endocytosed proteins are either delivered to the lysosome to be degraded or are exported from the endosomal system and delivered to other organelles. Sorting of the Saccharomyces cerevisiae reductive iron transporter, composed of the Fet3 and Ftr1 proteins, in the endosomal system is regulated by available iron; in iron-starved cells, Fet3-Ftr1 is sorted by Snx3/Grd19 and retromer into a recycling pathway that delivers it back to the plasma membrane, but when starved cells are exposed to iron, Fet3-Ftr1 is targeted to the lysosome-like vacuole and is degraded. We report that iron-induced endocytosis of Fet3-Ftr1 is independent of Fet3-Ftr1 ubiquitylation, and after endocytosis, degradation of Fet3-Ftr1 is mediated by the multivesicular body (MVB) sorting pathway. In mutant cells lacking any component of the ESCRT protein-dependent MVB sorting machinery, the Rsp5 ubiquitin ligase, or in wild-type cells expressing Fet3-Ftr1 lacking cytosolic lysyl ubiquitin acceptor sites, Fet3-Ftr1 is constitutively sorted into the recycling pathway independent of iron status. In the presence and absence of iron, Fet3-Ftr1 transits an endosomal compartment where a subunit of the MVB sorting receptor (Vps27), Snx3/Grd19, and retromer proteins colocalize. We propose that this endosome is where Rsp5 ubiquitylates Fet3-Ftr1 and where the recycling and degradative pathways diverge. INTRODUCTIONThe endocytic pathway is initiated with the internalization of protein and lipid cargo from the plasma membrane. After endocytosis, internalized molecules transit through the endosomal system, a network of interconnected organelles that process and sort cargo molecules back to the plasma membrane, to other organelles, or to lysosomes for degradation. In mammalian cells, early endosomes are pleiomorphic organelles composed of vacuolar domains that contain lumenal vesicles and tubular domains that lead into and emanate from the vacuolar portion. This distinct architecture has functional significance. The tubular elements of the organelle are regions where the majority of internalized plasma membrane proteins and lipids are exported and recycled from the endosomal system via bulk flow and cargo-specific processes (Mayor et al., 1993;Maxfield and McGraw, 2004;Bonifacino and Rojas, 2006). Cargo proteins that are not exported are delivered to lysosomes and many of these are degraded. This occurs via an active, signal-mediated event in which these proteins are targeted to the vacuolar region of the endosome where they are incorporated into vesicles that bud from the limiting membrane into the lumen of the organelle (Piper and Katzmann, 2007). During endosome maturation lumenal vesicles accrue until fusion of the late endosome with the lysosome results in degradation of these vesicles and their contents. A central sorting function of the endosomal system is thus to segregate cargo to be exported from the endosome from cargo to be degraded via lysosomal proteolysis.The core components of the recycling (retrograde) and degradative sorting pathways have be...

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Retromer Sorting

Small

2008

Arch Neurol

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uring the tail end of the 20th century, a "golden period" in Alzheimer disease (AD) research, many of the pathogenic molecules of the autosomal dominant form of the disease were isolated. These molecular defects, however, do not exist in "sporadic" late-onset AD, the form of the disease that accounts for more than 95% of all cases. Pinpointing the pathogenic molecules of late-onset AD has, therefore, become an urgent goal, both for understanding disease mechanisms and for opening up novel therapeutic avenues. The retromer sorting pathway transports cargo along the endosome-trans-Golgi network, and retromer defects were first implicated in late-onset AD by a study that combined brain imaging with microarray. A range of studies have confirmed that defects in this pathway can play a pathogenic role in the disease. Herein, these findings will be reviewed, the details of the retromer sorting pathway will be discussed, and a biological model that can account for the disease's regional selectivity will be elaborated.

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Human Orthologs of Yeast Vacuolar Protein Sorting Proteins Vps26, 29, and 35: Assembly into Multimeric Complexes

Cited by 284 publications

References 24 publications

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

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

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Retromer Sorting

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