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Pietro De Camilli - One of the best experts on this subject based on the ideXlab platform.

  • Epsin deficiency impairs endocytosis by stalling the actin dependent invagination of endocytic clathrin coated pits
    eLife, 2014
    Co-Authors: Mirko Messa, Theodora S. Ross, Hong Chen, Beverly Wendland, Ruben Fernandezbusnadiego, Elizabeth Wen Sun, Heather Czapla, Kristie Wrasman, Pietro De Camilli
    Abstract:

    Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate such function(s), we generated embryonic fibroblasts from conditional Epsin triple KO mice. Triple KO cells displayed a dramatic cell division defect. Additionally, a robust impairment in clathrin-mediated endocytosis was observed, with an accumulation of early and U-shaped pits. This defect correlated with a perturbation of the coupling between the clathrin coat and the actin cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results indicate that a key evolutionary conserved function of Epsin, in addition to other roles that include, as we show here, a low affinity interaction with SNAREs, is to help generate the force that leads to invagination and then fission of clathrin-coated pits.

  • Brief Report Epsin 1 Undergoes Nucleocytosolic Shuttling and its Eps15 Interactor NH 2-terminal Homology (ENTH) Domain, Structurally Similar to Armadillo and HEAT Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn 2 � Finger P
    2013
    Co-Authors: Joel Hyman, Pietro De Camilli, Hong Chen, Pier Paolo Di Fiore, Axel T. Brunger
    Abstract:

    Abstract. Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH 2-terminal portion of Epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (Epsin NH 2-terminal homology domain). We have now solved the crystal structure of rat Epsin 1 ENTH domain to 1.8 Å resolution. This domain is structurally similar to armadillo and Heat repeats of �-catenin and karyopherin-�, respectively. We have also identified and characterized the interaction of Epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn 2 � finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1dependent nuclear export pathway, induces an accumulation of Epsin 1 in the nucleus. These findings suggest that Epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function. Key words: clathrin • Eps15 homology domain • catenin • karyopherin • endocytosi

  • Epsin 1 Undergoes Nucleocytosolic Shuttling and Its Eps15 Interactor Nh2-Terminal Homology (Enth) Domain, Structurally Similar to Armadillo and Heat Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn2+ Finger Protein (Plzf)
    The Journal of cell biology, 2000
    Co-Authors: Joel Hyman, Pietro De Camilli, Hong Chen, Pier Paolo Di Fiore, Axel T. Brunger
    Abstract:

    Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH2-terminal portion of Epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (Epsin NH2-terminal homology domain). We have now solved the crystal structure of rat Epsin 1 ENTH domain to 1.8 A resolution. This domain is structurally similar to armadillo and Heat repeats of β-catenin and karyopherin-β, respectively. We have also identified and characterized the interaction of Epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn2+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of Epsin 1 in the nucleus. These findings suggest that Epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function.

  • Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF
    'Rockefeller University Press', 2000
    Co-Authors: Joel Hyman, Pietro De Camilli, Hong Chen, Pier Paolo Di Fiore, Axel T. Brunger
    Abstract:

    Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH(2)-terminal portion of Epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (Epsin NH(2)-terminal homology domain). We have now solved the crystal structure of rat Epsin 1 ENTH domain to 1.8 A resolution. This domain is structurally similar to armadillo and Heat repeats of beta-catenin and karyopherin-beta, respectively. We have also identified and characterized the interaction of Epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of Epsin 1 in the nucleus. These findings suggest that Epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function

  • the Epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module
    Journal of Biological Chemistry, 1999
    Co-Authors: J A Rosenthal, Hong Chen, Vladimir I Slepnev, Lorenzo Pellegrini, Anna Elisabetta Salcini, P P Di Fiore, Pietro De Camilli
    Abstract:

    Abstract Epsin (Epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (Epsin 2), which we have cloned from human and rat brain libraries. Epsin 1 and 2 are most similar in their NH2-terminal region, which represents a module (Epsin NH2 terminal homology domain, ENTH domain) found in a variety of other proteins of the data base. The multiple DPW motifs, typical of the central region of Epsin 1, are only partially conserved in Epsin 2. Both proteins, however, interact through this central region with the clathrin adaptor AP-2. In addition, we show here that both Epsin 1 and 2 interact with clathrin. The three NPF motifs of the COOH-terminal region of Epsin 1 are conserved in the corresponding region of Epsin 2, consistent with the binding of both proteins to Eps15. Epsin 2, like Epsin 1, is enriched in brain, is present in a brain-derived clathrin-coated vesicle fraction, is concentrated in the peri-Golgi region and at the cell periphery of transfected cells, and partially colocalizes with clathrin. High overexpression of green fluorescent protein-Epsin 2 mislocalizes components of the clathrin coat and inhibits clathrin-mediated endocytosis. The Epsins define a new protein family implicated in membrane dynamics at the cell surface.

Hong Chen - One of the best experts on this subject based on the ideXlab platform.

  • Epsins Negatively Regulate Aortic Endothelial Cell Function by Augmenting Inflammatory Signaling
    'MDPI AG', 2021
    Co-Authors: Yunzhou Dong, Xiaofeng Cai, Beibei Wang, Kui Cui, Sudarshan Bhattacharjee, Scott Wong, Douglas B. Cowan, Hong Chen
    Abstract:

    Background: The endothelial Epsin 1 and 2 endocytic adaptor proteins play an important role in atherosclerosis by regulating the degradation of the calcium release channel inositol 1,4,5-trisphosphate receptor type 1 (IP3R1). In this study, we sought to identify additional targets responsible for Epsin-mediated atherosclerotic endothelial cell activation and inflammation in vitro and in vivo. Methods: Atherosclerotic ApoE−/− mice and ApoE−/− mice with an endothelial cell-specific deletion of Epsin 1 on a global Epsin 2 knock-out background (EC-iDKO/ApoE−/−), and aortic endothelial cells isolated from these mice, were used to examine inflammatory signaling in the endothelium. Results: Inflammatory signaling was significantly abrogated by both acute (tumor necrosis factor-α (TNFα) or lipopolysaccharide (LPS)) and chronic (oxidized low-density lipoprotein (oxLDL)) stimuli in EC-iDKO/ApoE−/− mice and murine aortic endothelial cells (MAECs) isolated from Epsin-deficient animals when compared to ApoE−/− controls. Mechanistically, the Epsin ubiquitin interacting motif (UIM) bound to Toll-like receptors (TLR) 2 and 4 to potentiate inflammatory signaling and deletion of the Epsin UIM mitigated this interaction. Conclusions: The Epsin endocytic adaptor proteins potentiate endothelial cell activation in acute and chronic models of atherogenesis. These studies further implicate Epsins as therapeutic targets for the treatment of inflammation of the endothelium associated with atherosclerosis

  • Epsin deficiency impairs endocytosis by stalling the actin dependent invagination of endocytic clathrin coated pits
    eLife, 2014
    Co-Authors: Mirko Messa, Theodora S. Ross, Hong Chen, Beverly Wendland, Ruben Fernandezbusnadiego, Elizabeth Wen Sun, Heather Czapla, Kristie Wrasman, Pietro De Camilli
    Abstract:

    Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate such function(s), we generated embryonic fibroblasts from conditional Epsin triple KO mice. Triple KO cells displayed a dramatic cell division defect. Additionally, a robust impairment in clathrin-mediated endocytosis was observed, with an accumulation of early and U-shaped pits. This defect correlated with a perturbation of the coupling between the clathrin coat and the actin cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results indicate that a key evolutionary conserved function of Epsin, in addition to other roles that include, as we show here, a low affinity interaction with SNAREs, is to help generate the force that leads to invagination and then fission of clathrin-coated pits.

  • Brief Report Epsin 1 Undergoes Nucleocytosolic Shuttling and its Eps15 Interactor NH 2-terminal Homology (ENTH) Domain, Structurally Similar to Armadillo and HEAT Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn 2 � Finger P
    2013
    Co-Authors: Joel Hyman, Pietro De Camilli, Hong Chen, Pier Paolo Di Fiore, Axel T. Brunger
    Abstract:

    Abstract. Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH 2-terminal portion of Epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (Epsin NH 2-terminal homology domain). We have now solved the crystal structure of rat Epsin 1 ENTH domain to 1.8 Å resolution. This domain is structurally similar to armadillo and Heat repeats of �-catenin and karyopherin-�, respectively. We have also identified and characterized the interaction of Epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn 2 � finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1dependent nuclear export pathway, induces an accumulation of Epsin 1 in the nucleus. These findings suggest that Epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function. Key words: clathrin • Eps15 homology domain • catenin • karyopherin • endocytosi

  • Epsin 1 Undergoes Nucleocytosolic Shuttling and Its Eps15 Interactor Nh2-Terminal Homology (Enth) Domain, Structurally Similar to Armadillo and Heat Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn2+ Finger Protein (Plzf)
    The Journal of cell biology, 2000
    Co-Authors: Joel Hyman, Pietro De Camilli, Hong Chen, Pier Paolo Di Fiore, Axel T. Brunger
    Abstract:

    Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH2-terminal portion of Epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (Epsin NH2-terminal homology domain). We have now solved the crystal structure of rat Epsin 1 ENTH domain to 1.8 A resolution. This domain is structurally similar to armadillo and Heat repeats of β-catenin and karyopherin-β, respectively. We have also identified and characterized the interaction of Epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn2+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of Epsin 1 in the nucleus. These findings suggest that Epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function.

  • Epsin 1 undergoes nucleocytosolic shuttling and its eps15 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF
    'Rockefeller University Press', 2000
    Co-Authors: Joel Hyman, Pietro De Camilli, Hong Chen, Pier Paolo Di Fiore, Axel T. Brunger
    Abstract:

    Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH(2)-terminal portion of Epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (Epsin NH(2)-terminal homology domain). We have now solved the crystal structure of rat Epsin 1 ENTH domain to 1.8 A resolution. This domain is structurally similar to armadillo and Heat repeats of beta-catenin and karyopherin-beta, respectively. We have also identified and characterized the interaction of Epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of Epsin 1 in the nucleus. These findings suggest that Epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function

Axel T. Brunger - One of the best experts on this subject based on the ideXlab platform.

Joel Hyman - One of the best experts on this subject based on the ideXlab platform.

Pier Paolo Di Fiore - One of the best experts on this subject based on the ideXlab platform.