Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice.
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.
Chen
Hong
H
Howard Hughes Medical Institute, Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536, USA.
Ko
Genevieve
G
Zatti
Alessandra
A
Di Giacomo
Giuseppina
G
Liu
Lijuan
L
Raiteri
Elisabetta
E
Perucco
Ezio
E
Collesi
Chiara
C
Min
Wang
W
Zeiss
Caroline
C
De Camilli
Pietro
P
Cremona
Ottavio
O
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution
D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; C577774:Epn2 protein, mouse; D051880:Receptors, Notch; C114154:epsin