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Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13838-43. doi: 10.1073/pnas.0907008106. Epub 2009 Aug 5.

Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice.

Author information

1
Howard Hughes Medical Institute, Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536, USA.

Abstract

Epsins are endocytic adaptors with putative functions in general aspects of clathrin-mediated endocytosis as well as in the internalization of specific membrane proteins. We have now tested the role of the ubiquitously expressed epsin genes, Epn1 and Epn2, by a genetic approach in mice. While either gene is dispensable for life, their combined inactivation results in embryonic lethality at E9.5-E10, i.e., at the beginning of organogenesis. Consistent with studies in Drosophila, where epsin endocytic function was linked to Notch activation, developmental defects observed in epsin 1/2 double knockout (DKO) embryos recapitulated those produced by a global impairment of Notch signaling. Accordingly, expression of Notch primary target genes was severely reduced in DKO embryos. However, housekeeping forms of clathrin-mediated endocytosis were not impaired in cells derived from these embryos. These findings support a role of epsin as a specialized endocytic adaptor, with a critical role in the activation of Notch signaling in mammals.

PMID:
19666558
PMCID:
PMC2728981
DOI:
10.1073/pnas.0907008106
[Indexed for MEDLINE]
Free PMC Article

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