Curvature of clathrin-coated pits driven by epsin

Ford, M.G.J.; Mills, Ian G.; Peter, Brian J.; Vallis, Yvonne; Praefcke, Gerrit J. K.; Evans, Philip R.; McMahon, Harvey T.

doi:10.1038/nature01020

Cited by 944 publications

(1,171 citation statements)

References 27 publications

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“…Here we identified two new partners of Vps27p: Ent3p and Ent5p, two PtdIns(3,5)P 2 effectors required for ubiquitin-dependent protein sorting into the MVB. It has been proposed that a function of the epsin1 ENTH domain at the plasma membrane is to induce membrane curvature (Ford et al, 2002). Once bound to PtdIns(4,5)P 2 , the 8-helixfolded ENTH domain of epsin 1 rearranges and an additional ␣ helix is formed (␣0, Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it was recently shown that Vps27p is directly recruited to PtdIns(3)P-containing endosomes where it binds to ubiquitinated MVB cargoes and subsequently recruits the ESCRT-I complex (Bilodeau et al, 2003;Katzmann et al, 2003). This results in sorting of ubi- (Ford et al, 2002). Once bound to PtdIns(4,5)P 2 , the 8-helixfolded ENTH domain of epsin 1 rearranges and an additional ␣ helix is formed (␣0, Figure 1).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

mentioning

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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“…Ceci est bien illustré par les fréquents treillis plats de clathrine observés à la surface de nombreuses cellules [23]. Le rôle actif de certaines protéines capables de « sculpter » la membrane plasmique a été établi [24][25][26][27]. En revanche, parmi les protéines connues ayant ces propriétés, la plupart ont un rôle tardif lors de la transition, au moment où les puits de clathrine deviennent des vésicules.…”

Section: Induction Des Vésicules De Clathrine : Le Rôle Controversé Dunclassified

“…Lors d'expériences de tubulation in vitro, le domaine F-BAR de FCHo2 est capable de déformer des liposomes en tubes de diamètres allant de 130 à 18 nm selon la concentration de protéines [28]. Plusieurs autres protéines telles que l'amphi physine, SNX9, FBP17, l'endophiline et l'epsine sont impliquées dans la formation de vésicules de clathrine et ont la capacité d'induire une courbure de la membrane [25][26][27]31]. En revanche, toutes ces protéines ont un rôle plus tardif que les FCHo et n'induisent pas la nucléation des puits de clathrine.…”

Section: Comment Les Protéines Fcho Induisent-elles La Formation Des unclassified

Initiation de l’endocytose par vésicules de clathrine

Boucrot¹,

McMahon²

2011

Med Sci (Paris)

Self Cite

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“…Another protein, epsin, in fact plays a crucial role in inducing the curvature of the membrane. 24,26 The protein epsin has binding sites in the clathrin lattice and also directly interacts with the membrane. This dual interaction together with the dual interaction of an adaptor protein Ap180 with clathrin and the membrane (Ap180 tethers the clathrin coat to the membrane) is believed to induce the vesicle nucleation and anchor the clathrin lattice to the budding vesicle.…”

Section: Spatial Stochastic Model For Endocytotic Vesiclementioning

confidence: 99%

A Multiscale Computational Approach to Dissect Early Events in the Erb Family Receptor Mediated Activation, Differential Signaling, and Relevance to Oncogenic Transformations

et al. 2007

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Abstract-We describe a hierarchical multiscale computational approach based on molecular dynamics simulations, free energy-based molecular docking simulations, deterministic network-based kinetic modeling, and hybrid discrete/ continuum stochastic dynamics protocols to study the dimermediated receptor activation characteristics of the Erb family receptors, specifically the epidermal growth factor receptor (EGFR). Through these modeling approaches, we are able to extend the prior modeling of EGF-mediated signal transduction by considering specific EGFR tyrosine kinase (EGFRTK) docking interactions mediated by differential binding and phosphorylation of different C-terminal peptide tyrosines on the RTK tail. By modeling signal flows through branching pathways of the EGFRTK resolved on a molecular basis, we are able to transcribe the effects of molecular alterations in the receptor (e.g., mutant forms of the receptor) to differing kinetic behavior and downstream signaling response. Our molecular dynamics simulations show that the drug sensitizing mutation (L834R) of EGFR stabilizes the active conformation to make the system constitutively active. Docking simulations show preferential characteristics (for wildtype vs. mutant receptors) in inhibitor binding as well as preferential enhancement of phosphorylation of particular substrate tyrosines over others. We find that in comparison to the wildtype system, the L834R mutant RTK preferentially binds the inhibitor erlotinib, as well as preferentially phosphorylates the substrate tyrosine Y1068 but not Y1173. We predict that these molecular level changes result in preferential activation of the Akt signaling pathway in comparison to the Erk signaling pathway for cells with normal EGFR expression. For cells with EGFR over expression, the mutant over activates both Erk and Akt pathways, in comparison to wildtype. These results are consistent with qualitative experimental measurements reported in the literature. We discuss these consequences in light of how the network topology and signaling characteristics of altered (mutant) cell lines are shaped differently in relationship to native cell lines.

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Curvature of clathrin-coated pits driven by epsin

Cited by 944 publications

References 27 publications

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

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

Initiation de l’endocytose par vésicules de clathrine

A Multiscale Computational Approach to Dissect Early Events in the Erb Family Receptor Mediated Activation, Differential Signaling, and Relevance to Oncogenic Transformations

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