Hrs recruits clathrin to early endosomes

Raiborg, Camilla; Bache, Kristi Cecilie Gronvold; Mehlum, Anja; Stang, Espen; Stenmark, Harald

doi:10.1093/emboj/20.17.5008

Cited by 353 publications

(385 citation statements)

References 70 publications

Supporting

Mentioning

348

Contrasting

Unclassified

Order By: Relevance

“…Anti-Cbl (RF) and anti-EGFR (RK2) antibodies were described previously. Affinity-purified rabbit antibodies against recombinant Hrs have been described previously 16 . Mouse monoclonal antibodies against the human transferrin receptor (B3-25) were obtained from Boehringer Mannheim (Mannheim, Germany).…”

Section: Reagents Cells Plasmids and Antibodiesmentioning

confidence: 99%

“…S4c). The ability of Hrs to bind and recruit clathrin is thought to be important for its function as an endosomal sorting receptor 16 , and we considered the possibility that ubiquitination could affect clathrin recruitment to endosomes. However, overexpression of both Hrs and the Hrs-ubiquitin chimera equally recruited clathrin to early endosomes, whereas Hrs(1-706), which lacks the clathrin-binding C terminus, did not cause any clathrin recruitment (see Supplementary Information, Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of ubiquitin-binding proteins by monoubiquitination

et al. 2006

View full text Add to dashboard Cite

Proteins containing ubiquitin-binding domains (UBDs) interact with ubiquitinated targets and regulate diverse biological processes, including endocytosis, signal transduction, transcription and DNA repair 1-3 . Many of the UBD-containing proteins are also themselves monoubiquitinated, but the functional role and the mechanisms that underlie this modification are less well understood. Here, we demonstrate that monoubiquitination of the endocytic proteins Sts1, Sts2, Eps15 and Hrs results in intramolecular interactions between ubiquitin and their UBDs, thereby preventing them from binding in trans to ubiquitinated targets. Permanent monoubiquitination of these proteins, mimicked by the fusion of ubiquitin to their carboxyl termini, impairs their ability to regulate trafficking of ubiquitinated receptors. Moreover, we mapped the in vivo monoubiquitination site in Sts2 and demonstrated that its mutation enhances the Sts2-mediated effects of epidermal-growth-factor-receptor downregulation. We propose that monoubiquitination of ubiquitin-binding proteins inhibits their capacity to bind to and control the functions of ubiquitinated targets in vivo.The attachment of a single ubiquitin molecule (monoubiquitin) to a variety of cell-surface receptors is sufficient to drive their internalization and degradation 2,4-6 . Several endocytic adaptor proteins that control these processes -such as Eps15, epsins and Hrs -harbour one or more ubiquitin-binding domains (UBDs) that are able to recognize the ubiquitinated receptors and sort them along the endocytic pathway 2 . Interestingly, UBDs often mediate monoubiquitination of the proteins that contain them 2,3,7 . However, it is not yet understood whether and how monoubiquitination of ubiquitin-binding proteins may contribute to the regulation of their functions in vivo.The suppressors of T-cell receptor signalling (Sts) 1 and 2 are ubiquitin-binding proteins that suppress signalling via T-cell receptors 8 and regulate endocytic sorting of receptor tyrosine kinases 9,10 . Sts1 and Sts2

show abstract

Section: Reagents Cells Plasmids and Antibodiesmentioning

confidence: 99%

mentioning

confidence: 99%

Regulation of ubiquitin-binding proteins by monoubiquitination

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Five Ala and/or Gly residues (9,16,28,35) are highly conserved and are involved in the formation of an 'Alanine zipper' between the first two helixes (see Supplementary material Figure S4) [64]. The 'Alanine zipper' also participates in the coiled coil formation as a result of its interaction with aromatic and/or large hydrophobic side-chain residues as Leu, Tyr and Ile.…”

Section: Vps4mentioning

confidence: 99%

“…HIV, MuLV and RSV) and in lipid partitioning [7,8]. However, MVBs are also central for sorting vacuolar proteins directly from the late Golgi to the anterograde and biosynthetic pathway ( Figure 1) [9]. Furthermore, MVBs operate in the exocytotic pathway and the secreted interluminal vesicles are known as exosomes (Figure 1) [10][11][12].…”

mentioning

confidence: 99%

Exploring the ESCRTing machinery in eukaryotes

Winter

Hauser

2006

Trends in Plant Science

164

200

View full text Add to dashboard Cite

The profile of protein sorting into multivesicular bodies (MVBs) has risen recently with the identification of three heteromeric complexes known as ESCRT-I,-II,-III (Endosomal Sorting Complex Required for Transport). Genetic analyses in yeast have identified up to 15 soluble class E VPS (vacuolar protein sorting) proteins that have been assigned to the ESCRT machinery and function in cargo recognition and sorting, complex assembly, vesicle formation and dissociation. Despite their functional importance in yeast and mammalian cells, little is known about their presence and function in other organisms including plants. We have made use of the fully sequenced genomes of Arabidopsis thaliana and Oryza sativa, Drosophila melanogaster and Caenorhabditis elegans to explore the identity, structural characteristics and phylogenetic relationships of proteins assigned to the ESCRT machinery.Multivesicular bodies (MVBs) are late endosomal organelles with up to several hundred interluminal vesicles that originate by invagination and budding of the limiting endosomal membrane (Figure 1) [1,2]. MVBs are also prevacuolar compartments involved in the retrograde endocytotic pathway where, upon fusion to vacuoles or lysosomes, the interluminal vesicles are released [3][4][5][6]. In yeast and mammals, MVBs are involved in sorting and degradation of transmembrane surface proteins as transporters (e.g. GAP1, STE6 and PDR5), receptors (e.g. EGFR, GHR, STE3 and STE2), in budding of viruses (e.g. HIV, MuLV and RSV) and in lipid partitioning [7,8]. However, MVBs are also central for sorting vacuolar proteins directly from the late Golgi to the anterograde and biosynthetic pathway ( Figure 1) [9]. Furthermore, MVBs operate in the exocytotic pathway and the secreted interluminal vesicles are known as exosomes (Figure 1) [10][11][12]. Thus, MVBs act as an intermediate station for cargo on the way to degradation, intracellular recycling and secretion ( Figure 1). Although MVBs have been described in plants, little is known about their biogenesis, cargos and function [2,4,[13][14][15][16]. These studies show that plant MVBs are prevacuolar compartments and are labeled by vacuolar sorting receptor (VSR) antibodies such as BP80 [5,17]. Plant MVBs are not only involved in the transport of proteins to lytic but also to protein-storage vacuoles. As plasmalemmasomes in tobacco, MVBs have been implicated in the internalization of arabinogalactanrich plasma membrane proteins that are sequestered within the vacuole [18] Upstream cargo recognition and sorting system of the ESCRT machineryThe entry of membrane proteins into the MVB pathway starts with the binding of monoubiquitinated cargos to the outer endosomal membrane and the recruitment of the ESCRT-I complex. This membrane association is mediated by ubiquitin-binding proteins that contain one or two UIMs or a GAT domain in combination with protein domains that had been implicated in binding to membranes such as the phosphatidylinositol-3 phosphate (PI3P) binding FYVE finger domain (Figure...

show abstract

“…Based on the work with the dynamin specific GTP hydrolysis inhibitor dynasore, it was recently proposed that dynamin may in fact act at two different stages in clathrin-vesicle formation, (Macia et al, 2006). Using dynasore, the authors observed the arrest of clathrin-coated vesicle formation at two different stages, both Dynamin has been demonstrated to be involved in recycling from early endosomes to the TGN (Nicoziani et al, 2000) and dynamin has also been shown to be recruited to early endosomal clathrin coats upon overexpression of the endosomal sorting-protein Hrs (Raiborg et al, 2001a). Recycling of the TfR has been proposed to follow two distinct pathways, one pathway where dynamin is involved in transport from the early endosome to the recycling endosome, and another pathway different from that via the recycling endosome (van Dam et al, 2002).…”

Section: Dynaminmentioning

confidence: 99%