Selective high-level expression of epsin 3 in gastric parietal cells, where it is localized at endocytic sites of apical canaliculi.
Epsin is a ubiquitin-binding endocytic adaptor, which is highly concentrated at clathrin-coated pits and coordinates acquisition of bilayer curvature with coat recruitment and cargo selection. Epsin is encoded by three distinct genes in mammals. Epsin 1 and 2 have broad tissue distribution with high-level expression in the brain. In contrast, epsin 3 was reported to be expressed primarily in immature keratinocytes. Here, we show that epsin 3 is selectively expressed at high levels in the stomach (including the majority of gastric cancers), where it is concentrated in parietal cells. In these cells, epsin 3 is enriched and colocalized with clathrin around apical canaliculi, the sites that control acidification of the stomach lumen via the exo-endocytosis of vesicles containing the H/K ATPase. Deletion of the epsin 3 gene in mice did not result in obvious pathological phenotypes in either the stomach or other organs, possibly because of overlapping functions of the other two epsins. However, levels of EHD1 and EHD2, two membrane tubulating proteins with a role in endocytic recycling, were elevated in epsin 3 knock-out stomachs, pointing to a functional interplay of epsin 3 with EHD proteins in the endocytic pathway of parietal cells. We suggest that epsin 3 cooperates with other bilayer binding proteins with curvature sensing/generating properties in the specialized traffic and membrane remodeling processes typical of gastric parietal cells.
Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Genevieve
G
Ko
Summer
S
Paradise
Hong
H
Chen
Morven
M
Graham
Manuela
M
Vecchi
Fabrizio
F
Bianchi
Ottavio
O
Cremona
Pier Paolo
PP
Di Fiore
Pietro
P
De Camilli
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016764:Cell Polarity; D004705:Endocytosis / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000502:physiology* / Q000648:ultrastructure; D013270:Stomach / Q000033:anatomy & histology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C485117:EHD2 protein, mouse; C485640:Ehd1 protein, mouse; D033921:Vesicular Transport Proteins; C558122:epsin 3, mouse; D017506:H(+)-K(+)-Exchanging ATPase