Interactions of TOM1L1 with the Multivesicular Body Sorting Machinery

Puertollano, Rosa

doi:10.1074/jbc.m412481200

Cited by 69 publications

(72 citation statements)

References 63 publications

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“…At the plasma membrane, CEP55 (19)(20)(21) and the P(S/T)AP motifs of HIV-1 Gag (22)(23)(24)(25) and other viral proteins provide the additional increment in affinity to drive recruitment. In the case of endosomes, the P (S/T)AP of the Hrs subunit of ESCRT-0 and the proteins Tom1L1 and GGA3 could serve as additional factors providing specificity (26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Bouřa

Hurley

2012

Proc. Natl. Acad. Sci. U.S.A.

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MVB12-associated β-prism (MABP) domains are predicted to occur in a diverse set of membrane-associated bacterial and eukaryotic proteins, but their existence, structure, and biochemical properties have not been characterized experimentally. Here, we find that the MABP domains of the MVB12A and B subunits of ESCRT-I are functional modules that bind in vitro to liposomes containing acidic lipids depending on negative charge density. The MABP domain is capable of autonomously localizing to subcellular puncta and to the plasma membrane. The 1.3-Å atomic resolution crystal structure of the MVB12B MABP domain reveals a β-prism fold, a hydrophobic membrane-anchoring loop, and an electropositive phosphoinositide-binding patch. The basic patch is open, which explains how it senses negative charge density but lacks stereoselectivity. These observations show how ESCRT-I could act as a coincidence detector for acidic phospholipids and protein ligands, enabling it to function both in protein transport at endosomes and in cytokinesis and viral budding at the plasma membrane.HIV | protein structure | protein-membrane interactions | X-ray crystallography | subcellular localization T he concept of modular membrane-targeting domains is an important theme in the architecture of regulatory proteins and central to our current understanding of the subcellular localization of proteins (1-3). The best known of these modules include the PH, PX, FYVE, C1, C2, and ENTH domains (1-3). Each of these domains was initially proposed on the basis of bioinformatics analysis and subsequently confirmed by structural, biochemical, and cell biological approaches.A recent bioinformatics analysis (4) led to the identification of a putative membrane-targeted domain, termed the "MVB12-associated β-prism" (MABP) domain (4). MABP domains are found at the N termini of MVB12A and B, which are subunits of the human ESCRT-I complex (5). ESCRT complexes are responsible for the endosomal sorting of ubiquitinated membrane proteins into multivesicular bodies (MVBs) en route to their lysosomal degradation (6, 7). ESCRT-I in particular is also involved in plasma membrane functions in cytokinesis and the release of HIV-1 and other viruses (8). MABP domains are also found in many membrane-associated bacterial proteins and in the N-terminal region of human DENND4 isoforms. DENND4 proteins are Rab10 guanine nucleotide exchange factors that localize to a tubular Golgi-proximal membrane compartment (9).We set out to test the inference that MABP domains interact with membranes and found that the MVB12A and B MABP domains did. The crystal structure, solved at atomic resolution, showed that the MABP domain has a β-prism fold, consistent with the bioinformatics analysis. The structure identified a potential membrane-binding site, which we confirmed experimentally in vitro and in vivo. We found that the domain bound to liposomes according to the negative charge density of the membrane but with little specificity for particular lipid head groups. We went on to characterize the...

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Section: Discussionmentioning

confidence: 99%

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Bouřa

Hurley

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…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%

“…Also VPS27 and HRS contain clathrin-binding motifs and colocalize with flat 'bilayered' endosomal clathrin coats [26,37,38]. TOM1L1 interacts with HSR and the ubiquitin-binding protein TSG101 of the ESCRT-I complex [28]. Therefore, VSP27, HRS and TOM1 proteins might act as adaptor and concentrator molecules that interact with the flat endosomal clathrin coat and bind to both the monoubiquitinated transmembrane proteins and an ESCRT-I component.…”

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confidence: 99%

“…Current models for the function of the ESCRT machinery propose that monoubiquitinated membrane proteins are recognized by ubiquitin-binding proteins such as GGAs, VPS27 (yeast) or the mammalian ortholog HRS, HSE or STAM and the TOM1 families of proteins [28] (Figure 2). These proteins together with the endosomal clathrin-coat are likely to recognize cargo proteins and recruit ESCRT-I components from the cytoplasm.…”

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confidence: 99%

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Exploring the ESCRTing machinery in eukaryotes

Winter

Hauser

2006

Trends in Plant Science

164

200

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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...

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“…However, it is not known whether Vav proteins have a role in EGFR endocytosis or trafficking. Recently, in a proteomic study on multi-SH3 domain containing proteins, we identified two endosome-associated proteins that interacts with Vav2: the Rab regulatory protein Gapvd1 and the endosome-associated protein Tom1L1 (Puertollano, 2005;Bache et al, 2006;Hunker et al, 2006;Thalappilly et al, 2008). The aim of this work is to better understand the role of Vav2 in EGFR endocytosis and degradation in association with the endosomal proteins (Gapvd1 and Tom1L1).…”

Section: Introductionmentioning

confidence: 99%

VAV2 regulates epidermal growth factor receptor endocytosis and degradation

et al. 2010

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Vav proteins are guanine nucleotide exchange factors for Rho GTPases that regulate cell adhesion, motility, spreading and proliferation in response to growth factor signalling. In this work, we show that Vav2 expression delayed epidermal growth factor receptor (EGFR) internalization and degradation, and enhanced EGFR, ERK and Akt phosphorylations. This effect of Vav2 on EGFR degradation is dependent on its guanine nucleotide exchange function. Knockdown of Vav2 in HeLa cells enhanced EGFR degradation and reduced cell proliferation. epidermal growth factor stimulation led to colocalization of Vav2 with EGFR and Rab5 in endosomes. We further show that the effect of Vav2 on EGFR stability is modulated by its interaction with two endosome-associated proteins and require RhoA function. Thus, in this work, we report for the first time that Vav2 can regulate growth factors receptor signalling by slowing receptor internalization and degradation through its interaction with endosome-associated proteins.

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Interactions of TOM1L1 with the Multivesicular Body Sorting Machinery

Cited by 69 publications

References 63 publications

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit

Exploring the ESCRTing machinery in eukaryotes

VAV2 regulates epidermal growth factor receptor endocytosis and degradation

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