Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits

Mirko Messa, Rubén Fernández-Busnadiego, Elizabeth Wen Sun, Hong Chen, Heather Czapla, Kristie Wrasman, Yumei Wu, Genevieve Ko, Theodora Ross, Beverly Wendland, Pietro De Camilli

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e03311
JournaleLife
Volume3
DOIs
StatePublished - 2014

Fingerprint

Clathrin
Endocytosis
Actins
Vesicular Transport Adaptor Proteins
SNARE Proteins
Defects
Fibroblasts
Actin Cytoskeleton
Cell Division
Assays
Cells
epsin

Keywords

  • actin
  • clathrin-mediated endocytosis
  • cytokinesis
  • epsin
  • Hip1R
  • SNARE

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Messa, M., Fernández-Busnadiego, R., Sun, E. W., Chen, H., Czapla, H., Wrasman, K., ... De Camilli, P. (2014). Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits. eLife, 3, e03311. https://doi.org/10.7554/eLife.03311

Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits. / Messa, Mirko; Fernández-Busnadiego, Rubén; Sun, Elizabeth Wen; Chen, Hong; Czapla, Heather; Wrasman, Kristie; Wu, Yumei; Ko, Genevieve; Ross, Theodora; Wendland, Beverly; De Camilli, Pietro.

In: eLife, Vol. 3, 2014, p. e03311.

Research output: Contribution to journalArticle

Messa, M, Fernández-Busnadiego, R, Sun, EW, Chen, H, Czapla, H, Wrasman, K, Wu, Y, Ko, G, Ross, T, Wendland, B & De Camilli, P 2014, 'Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits', eLife, vol. 3, pp. e03311. https://doi.org/10.7554/eLife.03311
Messa, Mirko ; Fernández-Busnadiego, Rubén ; Sun, Elizabeth Wen ; Chen, Hong ; Czapla, Heather ; Wrasman, Kristie ; Wu, Yumei ; Ko, Genevieve ; Ross, Theodora ; Wendland, Beverly ; De Camilli, Pietro. / Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits. In: eLife. 2014 ; Vol. 3. pp. e03311.
@article{762516e809c74042968b945a6d7bcb06,
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.",
keywords = "actin, clathrin-mediated endocytosis, cytokinesis, epsin, Hip1R, SNARE",
author = "Mirko Messa and Rub{\'e}n Fern{\'a}ndez-Busnadiego and Sun, {Elizabeth Wen} and Hong Chen and Heather Czapla and Kristie Wrasman and Yumei Wu and Genevieve Ko and Theodora Ross and Beverly Wendland and {De Camilli}, Pietro",
year = "2014",
doi = "10.7554/eLife.03311",
language = "English (US)",
volume = "3",
pages = "e03311",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits

AU - Messa, Mirko

AU - Fernández-Busnadiego, Rubén

AU - Sun, Elizabeth Wen

AU - Chen, Hong

AU - Czapla, Heather

AU - Wrasman, Kristie

AU - Wu, Yumei

AU - Ko, Genevieve

AU - Ross, Theodora

AU - Wendland, Beverly

AU - De Camilli, Pietro

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - actin

KW - clathrin-mediated endocytosis

KW - cytokinesis

KW - epsin

KW - Hip1R

KW - SNARE

UR - http://www.scopus.com/inward/record.url?scp=84964698716&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964698716&partnerID=8YFLogxK

U2 - 10.7554/eLife.03311

DO - 10.7554/eLife.03311

M3 - Article

VL - 3

SP - e03311

JO - eLife

JF - eLife

SN - 2050-084X

ER -