Intectin, a Novel Small Intestine-specific Glycosylphosphatidylinositol-anchored Protein, Accelerates Apoptosis of Intestinal Epithelial Cells

Hidefumi Kitazawa,Tamao Nishihara,Tadahiro Nambu,Hitoshi Nishizawa,Masanori Iwaki,Atsunori Fukuhara,Toshio Kitamura,Morihiro Matsuda,Iichiro Shimomura

doi:10.1074/jbc.m408047200

Abstract

Intestinal epithelial cells undergo rapid turnover and exfoliation especially at the villus tips. This process is modulated by various nutrients especially fat. Apoptosis is one of the important regulatory mechanisms of this turnover. Therefore, identification of the factors that control epithelial cell apoptosis should help us understand the mechanism of intestinal mucosal turnover. Here, we report the identification of a novel small intestine-specific member of the Ly-6 family, intectin, by signal sequence trap method. Intectin mRNA expression was exclusively identified in the intestine and localized at the villus tips of intestinal mucosa, which is known to undergo apoptosis. Intectin mRNA expression was modulated by nutrition. Intestinal epithelial cells expressing intectin were more sensitive to palmitate-induced apoptosis, compared with control intestinal epithelial cells, and such effect was accompanied by increased activity of caspase-3. Intectin expression also reduced cell-cell adhesion of intestinal epithelial cells.

Highlights

Intestinal epithelial cells originate from stem cells at the base of the crypt and migrate along the crypt-villus axis toward the intestinal lumen
Identification of the factors that control epithelial cell apoptosis should help us understand the mechanism of intestinal mucosal turnover
When intestinal epithelial cells reach the luminal surface at the villus tips, they exfoliate into the lumen, and their cell cycle is terminated with a life span of only 3–5 days [1, 2]

Summary

Introduction

Intestinal epithelial cells originate from stem cells at the base of the crypt and migrate along the crypt-villus axis toward the intestinal lumen. Intectin mRNA expression was exclusively identified in the intestine and localized at the villus tips of intestinal mucosa, which is known to undergo apoptosis. Intestinal epithelial cells expressing intectin were more sensitive to palmitate-induced apoptosis, compared with control intestinal epithelial cells, and such effect was accompanied by increased activity of caspase-3.

Results

Conclusion