Antagonistic Roles of ESCRT and Vps Class C/HOPS Complexes in the Recycling of Yeast Membrane Proteins

Bugnicourt, Amandine; Froissard, Marine; Sereti, Kostianna; Ulrich, Helle D.; Haguenauer‐Tsapis, Rosine; Galan, Jean-Marc

doi:10.1091/mbc.e04-05-0420

Cited by 44 publications

(48 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B). The class C Vps complex has been shown to be involved in the recycling step of endocytosis, raising the possibility that the intracellular accumulation of Ras2 results from a defect in membrane recycling via an endosomal compartment (9). If this is true, then GFP-Ras2 should remain on the plasma membrane when endocytosis is blocked.…”

Section: Resultsmentioning

confidence: 99%

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Wang

Deschenes

2006

Molecular and Cellular Biology

View full text Add to dashboard Cite

Ras proteins are synthesized as cytosolic precursors, but then undergo posttranslational lipid addition, membrane association, and subcellular targeting to the plasma membrane. Although the enzymes responsible for farnesyl and palmitoyl lipid addition have been described, the mechanism by which these modifications contribute to the subcellular localization of Ras is not known. Following addition of the farnesyl group, Ras associates with the endoplasmic reticulum (ER), where palmitoylation occurs in Saccharomyces cerevisiae. The subsequent translocation of Ras from the ER to the plasma membrane does not require the classical secretory pathway or a functional Golgi apparatus. Vesicular and nonvesicular transport pathways for Ras proteins have been proposed, but the pathway is not known. Here we describe a genetic screen designed to identify mutants defective in Ras trafficking in S. cerevisiae. The screen implicates, for the first time, the class C VPS complex in Ras trafficking. Vps proteins are best characterized for their role in endosome and vacuole membrane fusion. However, the role of the class C Vps complex in Ras trafficking is distinct from its role in endosome and vacuole vesicle fusion, as a mitochondrial involvement was uncovered. Disruption of class C VPS genes results in mitochondrial defects and an accumulation of Ras proteins on mitochondrial membranes. Ras also fractionates with mitochondria in wild-type cells, where it is detected on the outer mitochondrial membrane by virtue of its sensitivity to protease treatment. These results point to a previously uncharacterized role of mitochondria in the subcellular trafficking of Ras proteins.

show abstract

Section: Resultsmentioning

confidence: 99%

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Wang

Deschenes

2006

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…The rapid destabilization of the internalized Jen1-K9R variant could not be easily explained. One possibility is that the amount of Jen1 observed at the plasma membrane could result from its endocytosis, followed by its recycling to the cell surface, since plasma membrane redistribution of endosomal targeted transporters was described in the case of the vps class E mutants (49,50) and corresponds to the physiological fate of some transporters in WT cells (51). In that case, the instability of the internalized K9R variant, upon glucose addition, would be due to an unexpected increase in internalization into MVBs or to a defect in recycling.…”

Section: Discussionmentioning

confidence: 99%

Glucose-induced Ubiquitylation and Endocytosis of the Yeast Jen1 Transporter

Paiva

Vieira

Nondier

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Protein ubiquitylation is essential for many events linked to intracellular protein trafficking. Despite the significance of this process, the molecular mechanisms that govern the regulation of ubiquitylation remain largely unknown. Plasma membrane transporters are subjected to tightly regulated endocytosis, and ubiquitylation is a key signal at several stages of the endocytic pathway. The yeast monocarboxylate transporter Jen1 displays glucose-regulated endocytosis. We show here that casein kinase 1-dependent phosphorylation and HECT-ubiquitin ligase Rsp5-dependent ubiquitylation are required for Jen1 endocytosis. Ubiquitylation and endocytosis of Jen1 are induced within minutes in response to glucose addition. Jen1 is modified at the cell surface by oligo-ubiquitylation with ubiquitin-Lys 63 linked chain(s), and Jen1-Lys 338 is one of the target residues. UbiquitinLys 63 -linked chain(s) are also required directly or indirectly to sort Jen1 into multivesicular bodies. Jen1 is one of the few examples for which ubiquitin-Lys 63 -linked chain(s) was shown to be required for correct trafficking at two stages of endocytosis: endocytic internalization and sorting at multivesicular bodies.Ubiquitylation is one of the most prevalent protein posttranslational modifications in eukaryotes. In addition to its role in promoting proteasomal degradation of target proteins, ubiquitylation has been shown to regulate multiple processes, including DNA repair, signaling, and intracellular trafficking. Ubiquitylation serves as a key signal mediating the internalization of plasma membrane receptors and transporters, followed by their intracellular transport and subsequent recycling or lysosomal/vacuolar degradation (1, 2). In Saccharomyces cerevisiae, transporters usually display both constitutive and accelerated endocytosis regulated by factors such as excess substrate, changes in nutrient availability, and stress conditions. Ubiquitylation of these cell surface proteins acts as a signal triggering their internalization (1). A single essential E3 4 ubiquitin ligase, Rsp5, has been implicated in the internalization of most, if not all, endocytosed proteins (3). Rsp5 is the unique member in S. cerevisiae of the HECT (homologous to E6AP COOH terminus)-ubiquitin ligases of the Nedd4/Rsp5 family (4). In a few cases, Rsp5-dependent cell surface ubiquitylation was shown to involve PY-containing adapters that bind to Rsp5 (5-7). Rsp5-mediated ubiquitylation is also required for sorting into multivesicular bodies (MVBs) of endosomal membrane proteins that come from either the plasma membrane (through endocytosis) or the Golgi (through vacuolar protein sorting (VPS) pathway) (8). Although much progress has been made in elucidating the mechanistic basis of various steps in protein trafficking, the precise requirement for a specific type and length of Ub chains at various stages of the endocytic pathway remains to be addressed.The ubiquitin profile needed for proper internalization has been established for some yeast membrane proteins (1). Th...

show abstract

“…A second complex, known as the retromer complex, is necessary for recycling of Vps10p and is composed of Vps35p, Vps29p, and Vps26p and the Vps5p-Vps17p sorting nexin dimer (Reddy and Seaman, 2001; and reviewed by Seaman, 2005). A third multisubunit tethering complex with a recently discovered role in the recycling of the uracil permease Fur4p (Bugnicourt et al, 2004) that was first identified as being involved in the docking and fusion of vacuolar and/or endosomal membranes is the class C Vps/homotypic fusion and vacuole protein sorting (HOPS) complex (reviewed by Wickner, 2002;Whyte and Munro, 2002). Proteins forming this complex include Pep3/ Vps18p, Pep5/Vps11p, Vps16p, Vps33p, Vam3p, and Ypt7 (Raymond et al, 1992, Whyte andMunro, 2002).…”

Section: Gap1p Recycling Does Not Depend On Other Known Pathways For mentioning

confidence: 99%

“…Although defects in cargo ubiquitination, recognition by ESCRT machinery, and deubiquitination at the MVEs may result in the accumulation of proteins in endosomal and perivacuolar membranes, recent studies indicate the existence of alternative pathways that allow recycling of plasma membrane proteins from the latest stages of lysosomal/ vacuolar sorting (Babst et al, 2000;Nikko et al, 2003;Bugnicourt et al, 2004;Pizzirusso and Chang, 2004).…”

Section: Introductionmentioning

confidence: 99%

Amino Acids Regulate Retrieval of the Yeast General Amino Acid Permease from the Vacuolar Targeting Pathway

Rubio‐Texeira

Kaiser

2006

MBoC

View full text Add to dashboard Cite

Intracellular sorting of the general amino acid permease (Gap1p) in Saccharomyces cerevisiae depends on availability of amino acids such that at low amino acid concentrations Gap1p is sorted to the plasma membrane, whereas at high concentrations Gap1p is sorted to the vacuole. In a genome-wide screen for mutations that affect Gap1p sorting we identified deletions in a subset of components of the ESCRT (endosomal sorting complex required for transport) complex, which is required for formation of the multivesicular endosome (MVE). Gap1p-GFP is delivered to the vacuolar interior by the MVE pathway in wild-type cells, but when formation of the MVE is blocked by mutation, Gap1p-GFP efficiently cycles from this compartment to the plasma membrane, resulting in unusually high permease activity at the cell surface. Importantly, cycling of Gap1p-GFP to the plasma membrane is blocked by high amino acid concentrations, defining recycling from the endosome as a major step in Gap1p trafficking under physiological control. Mutations in LST4 and LST7 genes, previously identified for their role in Gap1p sorting, similarly block MVE to plasma membrane trafficking of Gap1p. However, mutations in other recycling complexes such as the retromer had no significant effect on the intracellular sorting of Gap1p, suggesting that Gap1p follows a genetically distinct pathway for recycling. We previously found that Gap1p sorting from the Golgi to the endosome requires ubiquitination of Gap1p by an Rsp5p ubiquitin ligase complex, but amino acid abundance does not appear to significantly alter the accumulation of polyubiquitinated Gap1p. Thus the role of ubiquitination appears to be a signal for delivery of Gap1p to the MVE, whereas amino acid abundance appears to control the cycling of Gap1p from the MVE to the plasma membrane.

show abstract

Antagonistic Roles of ESCRT and Vps Class C/HOPS Complexes in the Recycling of Yeast Membrane Proteins

Cited by 44 publications

References 54 publications

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Plasma Membrane Localization of Ras Requires Class C Vps Proteins and Functional Mitochondria in Saccharomyces cerevisiae

Glucose-induced Ubiquitylation and Endocytosis of the Yeast Jen1 Transporter

Amino Acids Regulate Retrieval of the Yeast General Amino Acid Permease from the Vacuolar Targeting Pathway

Contact Info

Product

Resources

About