Lipid raft organization and function in the small intestinal brush border

Abstract

The enterocyte brush border of the small intestine is a highly specialized membrane designed to function both as a high capacity digestive/absorptive surface of dietary nutrients and a permeability barrier towards lumenal pathogens. It is characterized by an unusually high content of glycolipids (approximately 30% of the total microvillar membrane lipid), enabling the formation of liquid ordered microdomains, better known as lipid rafts. The glycolipid rafts are stabilized by galectin-4, a 36 kDa divalent lectin that cross-links galactosyl (and other carbohydrate) residues present on membrane lipids and several brush border proteins, including some of the major hydrolases. These supramolecular complexes are further stabilized by intelectin, a 35 kDa trimeric lectin that also functions as an intestinal lactoferrin receptor. As a result, brush border hydrolases, otherwise sensitive to pancreatic proteinases, are protected from untimely release into the gut lumen. Finally, anti-glycosyl antibodies, synthesized by plasma cells locally in the gut, are deposited on the brush border glycolipid rafts, protecting the epithelium from lumenal pathogens that exploit lipid rafts as portals for entry to the organism.