Vac14 Controls PtdIns(3,5) P 2 Synthesis and Fab1-Dependent Protein Trafficking to the Multivesicular Body

Dove, Stephen K.; McEwen, Robert; Mayes, Andrew E.; Hughes, David C.; Beggs, Jean D.; Michell, Robert H.

doi:10.1016/s0960-9822(02)00891-6

Cited by 124 publications

(233 citation statements)

References 56 publications

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“…We did not observe coIP between Fig4-Myc and Fig4-HA not between Fab1-Myc and Fab1-HA ( Figure 5D). In contrast, Vac14-FLAG was retrieved with HA-Vac14 by IP ( Figure 5D), which is consistent with yeast two-hybrid assays showing Vac14 -Vac14 interaction (not illustrated; Dove et al, 2002). Overall, these results indicate that Fab1, Vac14, and Fig4 can physically associate to form a membrane-bound protein assembly.…”

Section: The Fab1 Kinase Recruits Vac14 To the Vacuolesupporting

confidence: 85%

“…We first tested and confirmed Vac14 interaction with itself in vitro; T7-Vac14-HIS 6 was recovered with GST-Vac14 but not with GST coupled to glutathione-agarose beads ( Figure 7F). Similarly, T7-Fig4-HIS 6 bound to GST-Vac14 but not to GST alone ( Figure 7F) Dove et al, 2002).…”

Section: In Vitro Binding Between Vac14 Fig4 and A Grol-like Fragmementioning

confidence: 86%

“…These include Vac7, a transmembrane protein with no apparent orthologues outside of Fungi; and the conserved adaptor-like protein Vac14 (Bonangelino et al, 1997;Dove et al, 2002;Gary et al, 2002). In vac14⌬ and vac7⌬ cells, PtdIns(3,5)P 2 levels are severely reduced and exhibit a phenotype similar to fab1⌬ cells (Bonangelino et al, 1997;Dove et al, 2002;Gary et al, 2002). In contrast, deletion of ATG18 This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -04 -0405) on July 23, 2008. causes a drastic increase in PtdIns(3,5)P 2 levels (Dove et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

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et al. 2008

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Section: The Fab1 Kinase Recruits Vac14 To the Vacuolesupporting

confidence: 85%

Section: In Vitro Binding Between Vac14 Fig4 and A Grol-like Fragmementioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

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“…Tul1, a transmembrane ubiquitin ligase, is required for ubiquitination of certain vacuolar proteins that utilize the MVB pathway. Fab1 is the phosphatidylinositol(3)phosphate 5-kinase that makes phosphatidylinositol(3,5)P 2 (Dove et al, 2002). Proteins that are ubiquitin-dependent for transport, such as Cps1 and Phm5, are mislocalized on the vacuole-limiting membrane in fab1⌬ and tul1⌬ cells ( Figure 6B; Reggiori and Pelham, 2002).…”

Section: Sorting Of Ath1 Into the Mvb Pathway Is Ubiquitin-independentmentioning

confidence: 99%

The Transmembrane Domain of Acid Trehalase Mediates Ubiquitin-independent Multivesicular Body Pathway Sorting

Huang

Reggiori

Klionsky

2007

MBoC

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Trehalose serves as a storage source of carbon and plays important roles under various stress conditions. For example, in many organisms trehalose has a critical function in preserving membrane structure and fluidity during dehydration/ rehydration. In the yeast Saccharomyces cerevisiae, trehalose accumulates in the cell when the nutrient supply is limited but is rapidly degraded when the supply of nutrients is renewed. Hydrolysis of trehalose in yeast depends on neutral trehalase and acid trehalase (Ath1). Ath1 resides and functions in the vacuole; however, it appears to catalyze the hydrolysis of extracellular trehalose. Little is known about the transport route of Ath1 to the vacuole or how it encounters its substrate. Here, through the use of various trafficking mutants we showed that this hydrolase reaches its final destination through the multivesicular body (MVB) pathway. In contrast to the vast majority of proteins sorted into this pathway, Ath1 does not require ubiquitination for proper localization. Mutagenesis analyses aimed at identifying the unknown targeting signal revealed that the transmembrane domain of Ath1 contains the information sufficient for its selective sequestration into MVB internal vesicles. INTRODUCTIONTrehalose, a nonreducing disaccharide in which two glucose molecules are connected in an ␣-1,1-glycosidic linkage, was first found in the ergot of rye in 1832 (Kopp et al., 1993). This sugar is widely distributed in various organisms, including bacteria, fungi, plants, insects, and invertebrates (Elbein, 1974). It was originally believed that trehalose served only as a sugar and energy reserve in the cell; however, it is now known that this molecule also functions as a structural component, plays a role in transport, and is involved in signaling (Elbein et al., 2003). But the most significant function of trehalose is in providing membrane protection against different kinds of stress conditions, such as heat, freezing, dehydration, anoxia, and nutrient limitation (Crowe et al., 1984).Trehalose is quite common in yeast. In Saccharomyces cerevisiae, trehalose may constitute as much as 15-20% of its dry weight when growing in a stress environment. A strong correlation has been shown between trehalose content and stress resistance (Van Dijck et al., 1995). When yeast cells grow on rich carbon sources, they have a very low level of trehalose. In contrast, as they enter the stationary phase when nutrients are exhausted or during growth on nonfermentable carbon sources, the level of this disaccharide substantially increases. Conversely, when nutrients are resupplied, trehalose is rapidly mobilized (Nwaka and Holzer, 1998). The enzymes involved in synthesis and degradation of trehalose are the key regulators of these processes.Currently the best studied pathway of trehalose biosynthesis is the one that catalyzes UDP-glucose and glucose-6-phosphate into trehalose by trehalose-6-phosphate synthase and trehalose-phosphate-phosphatase activities (Thevelein, 1984). On the other hand, the degradation...

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“…We have recently reported that Ent3p is a specific PtdIns(3,5)P 2 effector involved in protein sorting at the MVB in yeast (Friant et al, 2003). Analysis of yeast mutants unable to synthesize PtdIns(3,5)P 2 , such as fab1, vac7, and vac14, revealed that this phospholipid is also required for sorting ubiquitinated cargoes into the MVB (Bonangelino et al, 1997;Odorizzi et al, 1998;Reggiori and Pelham, 2001;Dove et al, 2002).In this study we investigate the role of Ent5p that also specifically binds to PtdIns(3,5)P 2 . It is associated with the ubiquitin-binding protein Vps27p and together with Ent3p is required for ubiquitin-dependent protein sorting into the MVB.…”

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confidence: 99%

Ent5p Is Required with Ent3p and Vps27p for Ubiquitin-dependent Protein Sorting into the Multivesicular Body

Eugster¹,

Pécheur²,

Michel

et al. 2004

MBoC

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At the late endosomes, cargoes destined for the interior of the vacuole are sorted into invaginating vesicles of the multivesicular body. Both PtdIns(3,5)P 2 and ubiquitin are necessary for proper sorting of some of these cargoes. We show that Ent5p, a yeast protein of the epsin family homologous to Ent3p, localizes to endosomes and specifically binds to PtdIns(3,5)P 2 via its ENTH domain. In cells lacking Ent3p and Ent5p, ubiquitin-dependent sorting of biosynthetic and endocytic cargo into the multivesicular body is disrupted, whereas other trafficking routes to the vacuole are not affected. Ent3p and Ent5p are associated with Vps27p, a FYVE domain containing protein that interacts with ubiquitinated cargoes and is required for protein sorting into the multivesicular body. Therefore, Ent3p and Ent5p are the first proteins shown to be connectors between PtdIns(3,5)P 2 -and the Vps27p-ubiquitin-driven sorting machinery at the multivesicular body. INTRODUCTIONEndosomes are crossroads between the biosynthetic and the endocytic pathways. Here, proteins destined for the lysosome/vacuole are segregated away from proteins recycling back to the plasma membrane or to the Golgi apparatus. A critical membrane segregation and protein-sorting event takes place in late endosomes, regions of endosomal membranes invaginate and vesicles bud into the lumen of the organelle, giving rise to the multivesicular body (MVB;Felder et al., 1990). Mature MVB fuses with the vacuole/ lysosome releasing internal vesicles into its lumen and thereby exposing them to the activity of hydrolytic enzymes (Futter et al., 1996;Odorizzi et al., 1998). This mechanism allows a subset of endosomal membrane proteins to be sorted to the lumen of the lysosome/vacuole, whereas others are either selectively recycled back to the Golgi or to the plasma membrane, or they end up on the lysosomal/vacuolar membrane (Pelham, 2002). In yeast, the MVB pathway is crucial for the regulated turnover of pheromone receptors and of some permeases (Odorizzi et al., 1998). Further, biosynthetic transmembrane proteins such as carboxypeptidase S (Cps1p) and Phm5p follow this route to reach their final destination, the vacuolar lumen (Odorizzi et al., 1998;Reggiori and Pelham, 2001;Epple et al., 2003).Ubiquitination has been implicated as an endosomal-sorting signal. Cps1p and Phm5p ubiquitination is essential to target them into the vacuolar lumen after sorting at the MVB (Katzmann et al., 2001;Reggiori and Pelham, 2001). Potential cargo receptors responsible for recognition and recruitment of ubiquitinated cargo into MVB vesicles are class E Vps (vacuolar protein sorting) proteins. Class E mutants accumulate cargo destined for the vacuole in an exaggerated endosomal structure and all (currently identified) class E proteins are required for sorting at the MVB (Conibear and Stevens, 1998). Vps23p, a class E protein of the ESCRT-I complex (endosomal-sorting complex required for transport), carries an ubiquitin-conjugating (UBC)-like domain and interacts directly with ubiquitin i...

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Vac14 Controls PtdIns(3,5) P 2 Synthesis and Fab1-Dependent Protein Trafficking to the Multivesicular Body

Cited by 124 publications

References 56 publications

Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

Assembly of a Fab1 Phosphoinositide Kinase Signaling Complex Requires the Fig4 Phosphoinositide Phosphatase

The Transmembrane Domain of Acid Trehalase Mediates Ubiquitin-independent Multivesicular Body Pathway Sorting

Ent5p Is Required with Ent3p and Vps27p for Ubiquitin-dependent Protein Sorting into the Multivesicular Body

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