Yeast Ypt11 is targeted to recycling endosomes in mammalian cells

Kail, Mark; Hollinshead, Mike; Kaufmann, Miriam; Boettcher, J.; Vaux, David J.; Barnekow, Angelika

doi:10.1042/bc20040139

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…Overall, GFP-Ypt11p localized to the ER and ERGIC in mammalian cells. We found no significant colocalization with markers of recycling endosomes, a localization that has recently been proposed for Ypt11p in mammalian cells (33), or with mitochondria, which have been functionally correlated with Ypt11p expression (6, 30) (data not shown). Overall, our data demonstrate that Ypt11p is located on the ER and enriched in the peripheral ER of the daughter cell, suggestive of the functions in this organelle.…”

Section: Vol 26 2006 Evolutionary Conservation Of Rab Localization mentioning

confidence: 71%

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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Section: Vol 26 2006 Evolutionary Conservation Of Rab Localization mentioning

confidence: 71%

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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“…As a result of these properties, histidine-containing polymers and their cargo are likely to escape enzymatic degradation by lysosomes. Furthermore, the endocytic pathways of yeast and mammalian cells have many similarities (21,30,35,36,38). Although the role of histidine has not been previously appreciated in buffering and lysing yeast endosomes, we think this mechanism has a significant role in transporting histidine-rich peptides (e.g., histatin 5 and H2K4b).…”

Section: Discussionmentioning

confidence: 88%

Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

Zhu

Luther

Leng

et al. 2006

Antimicrob Agents Chemother

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A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4-diisothiocyanato-stilbene-2,2-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

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“…So far, a role of the TGN in cargo recycling has been only marginally studied ( Csaba et al, 2007 ; Escola et al, 2010 ; Cheng and Filardo, 2012 ). The finding that Ypt32, a yeast TGN-localized Rab protein involved in recycling from the TGN to the cell surface, localizes to recycling endosomes in mammalian cells and affects transferrin receptor recycling ( Kail et al, 2005 ) suggests that recycling from endosomes and the TGN may be evolutionary related. Our work in yeast further indicates that this may be an ancestral mode of regulation, and provides insights into the molecular mechanism by which it is achieved.…”

Section: Discussionmentioning

confidence: 99%

Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5

Becuwe

Léon

2014

eLife

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After endocytosis, membrane proteins can recycle to the cell membrane or be degraded in lysosomes. Cargo ubiquitylation favors their lysosomal targeting and can be regulated by external signals, but the mechanism is ill-defined. Here, we studied the post-endocytic trafficking of Jen1, a yeast monocarboxylate transporter, using microfluidics-assisted live-cell imaging. We show that the ubiquitin ligase Rsp5 and the glucose-regulated arrestin-related trafficking adaptors (ART) protein Rod1, involved in the glucose-induced internalization of Jen1, are also required for the post-endocytic sorting of Jen1 to the yeast lysosome. This new step takes place at the trans-Golgi network (TGN), where Rod1 localizes dynamically upon triggering endocytosis. Indeed, transporter trafficking to the TGN after internalization is required for their degradation. Glucose removal promotes Rod1 relocalization to the cytosol and Jen1 deubiquitylation, allowing transporter recycling when the signal is only transient. Therefore, nutrient availability regulates transporter fate through the localization of the ART/Rsp5 ubiquitylation complex at the TGN.DOI: http://dx.doi.org/10.7554/eLife.03307.001

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Yeast Ypt11 is targeted to recycling endosomes in mammalian cells

Cited by 7 publications

References 27 publications

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

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

Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5

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