Selective high-level expression of epsin 3 in gastric parietal cells, where it is localized at endocytic sites of apical canaliculi

Genevieve Ko, Summer Paradise, Hong Chen, Morven Graham, Manuela Vecchi, Fabrizio Bianchi, Ottavio Cremona, Pier Paolo Di Fiore, Pietro De Camilli

Research output: Contribution to journalArticlepeer-review

Abstract

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 knockout 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.

Original languageEnglish
Pages (from-to)21511-21516
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
Publication statusPublished - Dec 14 2010

Keywords

  • Adaptor protein
  • EH domain
  • Ezrin
  • Gastric cancer
  • Hip1R

ASJC Scopus subject areas

  • General

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