title: Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits.
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.
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Mirko
authors.initials: M
authors.lastname: Messa
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández-Busnadiego
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Elizabeth Wen
authors.initials: EW
authors.lastname: Sun
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Czapla
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: Kristie
authors.initials: K
authors.lastname: Wrasman
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Ko
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, United States.
authors.forename: Theodora
authors.initials: T
authors.lastname: Ross
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, United States.
authors.forename: Beverly
authors.initials: B
authors.lastname: Wendland
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States pietro.decamilli@yale.edu.
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D061251:Primary Cell Culture; D011485:Protein Binding; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000199:Actins; D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D050600:SNARE Proteins; C114154:epsin
keywords: Hip1R; SNARE; actin; clathrin-mediated endocytosis; cytokinesis; epsin