Lipid raft organization and function in brush borders of epithelial cells.
Polarized epithelial cells of multicellular organisms confront the environment with a highly specialized apical cell membrane that differs in composition and function from that facing the internal milieu. In the case of absorptive cells, such as the small intestinal enterocyte and the kidney proximal tubule cell, the apical cell membrane is formed as a brush border, composed of regular, dense arrays of microvilli. Hydrolytic ectoenzymes make up the bulk of the microvillar membrane proteins, endowing the brush border with a huge digestive capacity. Several of the major enzymes are localized in lipid rafts, which, for the enterocyte in particular, are organized in a unique fashion. Glycolipids, rather than cholesterol, together with the divalent lectin galectin-4, define these rafts, which are stable and probably quite large. The architecture of these rafts supports a digestive/absorptive strategy for nutrient assimilation, but also serves as a portal for a large number of pathogens. Caveolae are well-known vehicles for internalization of lipid rafts, but in the enterocyte brush border, binding of cholera toxin is followed by uptake via a clathrin-dependent mechanism. Recently, 'anti-glycosyl' antibodies were shown to be deposited in the enterocyte brush border. When the antibodies were removed from the membrane, other carbohydrate-binding proteins, including cholera toxin, increased their binding to the brush border. Thus, anti-glycosyl antibodies may serve as guardians of glycolipid-based rafts, protecting them from lumenal pathogens and in this way be part of an ongoing 'cross-talk' between indigenous bacteria and the host.
Danielsen
E Michael
EM
Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark.
Hansen
Gert H
GH
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D002241:Carbohydrates / Q000276:immunology; D016764:Cell Polarity; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D037541:Galectin 4 / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008871:Microvilli / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure
D000906:Antibodies; D002241:Carbohydrates; D037541:Galectin 4; D006017:Glycolipids