TableEdit

Chen, H, Ko, G, Zatti, A, Di Giacomo, G, Liu, L, Raiteri, E, Perucco, E, Collesi, C, Min, W, Zeiss, C, De Camilli, P and Cremona, O (2009) Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice. Proc. Natl. Acad. Sci. U.S.A. 106:13838-43

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.

PubMed PMC2728981 Online version:10.1073/pnas.0907008106

Adaptor Proteins, Vesicular Transport/metabolism; Adaptor Proteins, Vesicular Transport/physiology; Animals; Clathrin/metabolism; Endocytosis; Fibroblasts/metabolism; Gene Expression Regulation, Developmental; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Genetic; Phenotype; Receptors, Notch/metabolism; Signal Transduction; Time Factors; Tissue Distribution