Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

Mayers, Jonathan R.; Wang, Lei; Pramanik, Jhuma; Johnson, Adam; Sarkeshik, Ali; Wang, Yueju; Saengsawang, Witchuda; Yates, John R.; Audhya, Anjon

doi:10.1073/pnas.1302918110

Cited by 61 publications

(101 citation statements)

References 44 publications

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“…Epsin favors binding to K63-polyubiquitin, which correlates well with the requirement of multiple Ubs as an internalization signal (Hawryluk et al 2006;Sato et al 2009). Other UBDs are present at sites of CME including ones in CIN85 and Hrs, and others are likely to be uncovered (Soubeyran et al 2002;Stamenova et al 2007;Mayers et al 2013). Because relatively few proteins have been assessed for Ub-dependent internalization, it is possible that these additional UBD-containing proteins operate as adaptors for different subsets of ubiquitinated proteins.…”

Section: How Ubiquitin Mediates Internalization From the Plasma Membranementioning

confidence: 99%

Ubiquitin-Dependent Sorting in Endocytosis

Piper

Đikić

Lukacs

2014

Cold Spring Harbor Perspectives in Biology

193

176

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When ubiquitin (Ub) is attached to membrane proteins on the plasma membrane, it directs them through a series of sorting steps that culminate in their delivery to the lumen of the lysosome where they undergo complete proteolysis. Ubiquitin is recognized by a series of complexes that operate at a number of vesicle transport steps. Ubiquitin serves as a sorting signal for internalization at the plasma membrane and is the major signal for incorporation into intraluminal vesicles of multivesicular late endosomes. The sorting machineries that catalyze these steps can bind Ub via a variety of Ub-binding domains. At the same time, many of these complexes are themselves ubiquitinated, thus providing a plethora of potential mechanisms to regulate their activity. Here we provide an overview of how membrane proteins are selected for ubiquitination and deubiquitination within the endocytic pathway and how that ubiquitin signal is interpreted by endocytic sorting machineries. HOW PROTEINS ARE SELECTED FOR UBIQUITINATIONU biquitin (Ub) is covalently attached to substrate proteins by the concerted action of E2-conjugating enzymes and E3 ligases (Varshavsky 2012). Most of the specificity and regulation of ubiquitination is at the level of the E3 ligases, which vastly outnumber the E2-conjugating enzymes. Ubiquitination results from the transfer of Ub, held either by the E2 or in some cases by the E3 as a high-energy thioester bond, onto a substrate protein, typically on the terminal amide of a substrate acceptor lysine side chain. Owing to the intense interest in the ubiquitination system, many of the simple rules and distinctions concerning different types of ligases, their specificity for forming particular polyUb chains, and even the kinds of residues in substrate proteins that can be ubiquitin modified, have been blurred with the discovery of mixed poly-Ub chains, new enzymatic mechanisms for Ub transfer, and ubiquitination of nonlysine residues (Kulathu and Komander 2012;Wenzel and Klevit 2012;McDowell and Philpott 2013). Nonetheless, in basic terms, Ub ligases function as platforms that coordinate substrate recognition with Ub transfer as well as configuring poly-Ub chain topology by the E2-conjugating enzyme. Substrates can be bound directly by the E3 ligase or by adaptor proteins that in turn bind to ligases, and selecEditors:

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Section: How Ubiquitin Mediates Internalization From the Plasma Membranementioning

confidence: 99%

Ubiquitin-Dependent Sorting in Endocytosis

Piper

Đikić

Lukacs

2014

Cold Spring Harbor Perspectives in Biology

193

176

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“…Interestingly, Mayers et al (2013) identified a FEI complex that seems to recruit ESCRT-0 to a subset of clathrin coated pits on the plasma membrane in Caenorhabditis elegans. Loss of the complex does not affect the overall rate of clathrin-mediated endocytosis but specifically inhibits degradation of lysosomal cargo.…”

Section: Tols: Coupling Endocytosis and Lysosomal Degradationmentioning

confidence: 99%

Helping Hands for Budding Prospects: ENTH/ANTH/VHS Accessory Proteins in Endocytosis, Vacuolar Transport, and Secretion

Zouhar

Sauer

2014

The Plant Cell

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Coated vesicles provide a major mechanism for the transport of proteins through the endomembrane system of plants. Transport between the endoplasmic reticulum and the Golgi involves vesicles with COPI and COPII coats, whereas clathrin is the predominant coat in endocytosis and post-Golgi trafficking. Sorting of cargo, coat assembly, budding, and fission are all complex and tightly regulated processes that involve many proteins. The mechanisms and responsible factors are largely conserved in eukaryotes, and increasing organismal complexity tends to be associated with a greater numbers of individual family members. Among the key factors is the class of ENTH/ANTH/VHS domain-containing proteins, which link membrane subdomains, clathrin, and other adapter proteins involved in early steps of clathrin coated vesicle formation. More than 30 Arabidopsis thaliana proteins contain this domain, but their generally low sequence conservation has made functional classification difficult. Reports from the last two years have greatly expanded our knowledge of these proteins and suggest that ENTH/ANTH/VHS domain proteins are involved in various instances of clathrin-related endomembrane trafficking in plants. This review aims to summarize these new findings and discuss the broader context of clathrin-dependent plant vesicular transport.

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“…Because CAV-1-GFP contains 34 lysine residues in its cytosolic region, it could be ubiquitylated at multiple sites. In fact, a recent study using mass spectrometry suggested that at least two lysine residues in GFP-CAV-1 are ubiquitylated in embryos (Mayers et al, 2013). To confirm that the smeared bands corresponded to the ubiquitylated form, CAV-1-GFP was immunoprecipitated from embryo lysates and probed with an anti-ubiquitin antibody (Fig.…”

Section: Cav-1-gfp Is Ubiquitylated After Fertilizationmentioning

confidence: 99%

Fertilization-induced K63-linked ubiquitylation mediates clearance of maternal membrane proteins

et al. 2014

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In Caenorhabditis elegans, fertilization triggers endocytosis and rapid turnover of maternal surface membrane proteins in lysosomes, although the precise mechanism of this inducible endocytosis is unknown. We found that high levels of K63-linked ubiquitin chains transiently accumulated on endosomes upon fertilization. Endocytosis and the endosomal accumulation of ubiquitin were both regulated downstream of the anaphase-promoting complex, which drives the oocyte's meiotic cell cycle after fertilization. The clearance of maternal membrane proteins and the accumulation of K63-linked ubiquitin on endosomes depended on UBC-13 and UEV-1, which function as an E2 complex that specifically mediates chain elongation of K63-linked polyubiquitin. CAV-1-GFP, an endocytic cargo protein, was modified with K63-linked polyubiquitin in a UBC-13/UEV-1-dependent manner. In ubc-13 or uev-1 mutants, CAV-1-GFP and other membrane proteins were internalized from the plasma membrane normally after fertilization. However, they were not efficiently targeted to the multivesicular body (MVB) pathway but recycled to the cell surface. Our results suggest that UBC-13-dependent K63-linked ubiquitylation is required for proper MVB sorting rather than for internalization. These results also demonstrate a developmentally controlled function of K63-linked ubiquitylation.

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Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

Cited by 61 publications

References 44 publications

Ubiquitin-Dependent Sorting in Endocytosis

Ubiquitin-Dependent Sorting in Endocytosis

Helping Hands for Budding Prospects: ENTH/ANTH/VHS Accessory Proteins in Endocytosis, Vacuolar Transport, and Secretion

Fertilization-induced K63-linked ubiquitylation mediates clearance of maternal membrane proteins

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