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Elife. 2014 Aug 13;3:e03311. doi: 10.7554/eLife.03311.

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

Author information

1
Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
2
Department of Biology, Johns Hopkins University, Baltimore, United States.
3
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, United States.
4
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.

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:

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

PMID:
25122462
PMCID:
PMC4161027
DOI:
10.7554/eLife.03311
[Indexed for MEDLINE]
Free PMC Article

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