Transferrin receptor-like proteins control the degradation of a yeast metal transporter

Stimpson, Helen E. M.; Lewis, Michael; Pelham, Hugh R.B.

doi:10.1038/sj.emboj.7600984

Cited by 83 publications

(127 citation statements)

References 41 publications

(62 reference statements)

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“…Bsd2 functions as an adaptor that directs Rsp5 activity toward proteins (such as CPS) that contain polar amino acids in their transmembrane domains (Hettema et al, 2004;Stimpson et al, 2006). Sna3 does not contain polar residues in either of its two transmembrane domains, consistent with our results indicating that neither its polyubiquitination nor its MVB sorting require Bsd2.…”

Section: Discussionsupporting

confidence: 89%

“…fore, is mediated by Rsp5 and not Tul1. However, Rsp5 activity toward Sna3 does not require Bsd2, which serves as an adaptor protein that couples Rsp5 to certain types of MVB cargoes, including CPS (Hettema et al, 2004;Stimpson et al, 2006), because the level of polyubiquitinated Sna3-GFP is unaffected by deletion of the BSD2 gene (bsd2⌬; Figure 2B). In addition, Sna3-GFP was correctly sorted via the MVB pathway in bsd2⌬ mutant cells, unlike GFP-CPS, which was mislocalized in the absence of Bsd2 ( Figure 2C).…”

Section: Rsp5 Directs Ub-independent Sortingmentioning

confidence: 99%

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Direct Binding to Rsp5 Mediates Ubiquitin-independent Sorting of Sna3 via the Multivesicular Body Pathway

McNatt

McKittrick

West

et al. 2007

MBoC

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The sorting of most integral membrane proteins into the lumenal vesicles of multivesicular bodies (MVBs) is dependent on the attachment of ubiquitin (Ub) to their cytosolic domains. However, Ub is not required for sorting of Sna3, an MVB vesicle cargo protein in yeast. We show that Sna3 circumvents Ub-mediated recognition by interacting directly with Rsp5, an E3 Ub ligase that catalyzes monoubiquitination of MVB vesicle cargoes. The PPAY motif in the C-terminal cytosolic domain of Sna3 binds the WW domains in Rsp5, and Sna3 is polyubiquitinated as a consequence of this association. However, Ub does not appear to be required for transport of Sna3 via the MVB pathway because its sorting occurs under conditions in which its ubiquitination is impaired. Consistent with Ub-independent function of the MVB pathway, we show by electron microscopy that the formation of MVB vesicles does not require Rsp5 E3 ligase activity. However, cells expressing a catalytically disabled form of Rsp5 have a greater frequency of smaller MVB vesicles compared with the relatively broad distribution of vesicles seen in MVBs of wild-type cells, suggesting that the formation of MVB vesicles is influenced by Rsp5-mediated ubiquitination. INTRODUCTIONMultivesicular bodies (MVBs) are late endosomes containing lumenal vesicles that are formed by invagination of the endosomal membrane. The lumenal MVB vesicles are delivered into the hydrolytic interior of the lysosome upon fusion of the limiting MVB membrane with the lysosomal membrane (van Deurs et al., 1995;Futter et al., 1996;Mullock et al., 1998). Many cell-surface receptors that undergo down-regulation from the plasma membrane are sorted into MVB vesicles en route to being degraded in the lysosome, including members of the receptor tyrosine kinase family in metazoans and G protein-coupled receptors in the budding yeast Saccharomyces cerevisiae. In yeast, many biosynthetic proteins are also sorted into MVB vesicles during their transport from the Golgi to the vacuole, the functional equivalent of the lysosome (reviewed in Hicke and Dunn, 2003).Most integral membrane proteins require the attachment of a single ubiquitin (Ub) to their cytosolic domains in order to be sorted into the MVB pathway (Katzmann et al., 2001;Reggiori and Pelham, 2001;Urbanowski and Piper, 2001). Sorting of monoubiquitinated MVB cargoes is mediated by a highly conserved machinery comprised of class E Vps proteins, many of which assemble into distinct endosomal sorting complexes required for transport (ESCRTs) that contain Ub-binding domains (reviewed in Hurley and Emr, 2006). In addition to Ub-mediated cargo recognition, class E Vps proteins are generally required for MVB vesicle budding because cells in which class E Vps proteins are disrupted contain malformed late endosomes that lack lumenal vesicles (Rieder et al., 1996;Odorizzi et al., 1998;Doyotte et al., 2005).The class E Vps/ESCRT machinery is also required for the budding of many nonlytic enveloped viruses from infected host cells, which is topologically equival...

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Section: Discussionsupporting

confidence: 89%

Section: Rsp5 Directs Ub-independent Sortingmentioning

confidence: 99%

Direct Binding to Rsp5 Mediates Ubiquitin-independent Sorting of Sna3 via the Multivesicular Body Pathway

McNatt

McKittrick

West

et al. 2007

MBoC

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“…6 and 7). This THNX 6 YGL sequence differed from the sequence that was required for the sorting of Pep12 from the TGN to late endosomes, FSDSPEF (45). Although mutations in these two tripeptides produced mis-sorting of Arn1 that was phenotypically similar to that of the GGA2 deletion, the phenotypes were not identical.…”

Section: Role Of Ubiquitination In the Vacuolar Protein Sorting Of Arn1-mentioning

confidence: 96%

“…The Menkes and Wilson copper transporters, ATP7A and ATP7B, relocalize in response to changes in intracellular copper (3). In yeast, transporters such as the general amino acid permease Gap1p (4), the manganese transporter Smf1p (5,6), and the ferrichrome (FC) 5 transporter Arn1p (7) undergo altered trafficking in response to changes in amino acid, manganese, and FC levels, respectively.…”

mentioning

confidence: 99%

Gga2 Mediates Sequential Ubiquitin-independent and Ubiquitin-dependent Steps in the Trafficking of ARN1 from the trans-Golgi Network to the Vacuole

Deng¹,

Guo²,

Watson

et al. 2009

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, ARN1 encodes a transporter for the uptake of ferrichrome, an important nutritional source of iron. In the absence of ferrichrome, Arn1p is sorted directly from the trans-Golgi network (TGN) to the vacuolar lumen via the vacuolar protein-sorting pathway. Arn1p is mis-sorted to the plasma membrane in cells lacking Gga2p, a monomeric clathrin-adaptor protein involved in vesicular transport from the TGN. Although Ggas have been characterized as ubiquitin receptors, we show here that ubiquitin binding by Gga2 was not required for the TGN-to-endosome trafficking of Arn1, but it was required for subsequent sorting of Arn1 into the multivesicular body. In a ubiquitin-binding mutant of Gga2, Arn1p accumulated on the vacuolar membrane in a ubiquitinated form. The yeast epsins Ent3p and Ent4p were also involved in TGN-to-vacuole sorting of Arn1p. Amino-terminal sequences of Arn1p were required for vacuolar protein sorting, as mutation of ubiquitinatable lysine residues resulted in accumulation on the vacuolar membrane, and mutation of either a THN or YGL sequence resulted in mis-sorting to the plasma membrane. These studies suggest that Gga2 is involved in sorting at both the TGN and multivesicular body and that the first step can occur without ubiquitin binding.

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“…For example, the adaptors Bul1 and Bul2 work both at the plasma membrane and the trans-Golgi (Nikko and Pelham 2009). The Art1-Art10 proteins (Lin et al 2008;Nikko and Pelham 2009;MacGurn et al 2011) function mainly at the plasma membrane, while the Rsp5 adaptor proteins Ear1, Ssh4, Bsd2, Tre1, and Tre2 are located mainly at endosomes (Liu et al 1997;Stimpson et al 2006;Leon et al 2008). Nutrient uptake is controlled by a regulatory loop that adjusts the level of amino acid transporters at the plasma membrane through Art1.…”

Section: Ubiquitin Function In Endocytosismentioning

confidence: 99%

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

et al. 2012

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Protein modifications provide cells with exquisite temporal and spatial control of protein function. Ubiquitin is among the most important modifiers, serving both to target hundreds of proteins for rapid degradation by the proteasome, and as a dynamic signaling agent that regulates the function of covalently bound proteins. The diverse effects of ubiquitylation reflect the assembly of structurally distinct ubiquitin chains on target proteins. The resulting ubiquitin code is interpreted by an extensive family of ubiquitin receptors. Here we review the components of this regulatory network and its effects throughout the cell.

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Transferrin receptor-like proteins control the degradation of a yeast metal transporter

Cited by 83 publications

References 41 publications

Direct Binding to Rsp5 Mediates Ubiquitin-independent Sorting of Sna3 via the Multivesicular Body Pathway

Direct Binding to Rsp5 Mediates Ubiquitin-independent Sorting of Sna3 via the Multivesicular Body Pathway

Gga2 Mediates Sequential Ubiquitin-independent and Ubiquitin-dependent Steps in the Trafficking of ARN1 from the trans-Golgi Network to the Vacuole

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

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