title: The dual role of annexin II in targeting of brush border proteins and in intestinal cell polarity.
abstract: Functional intestinal epithelium relies on complete polarization of enterocytes marked by the formation of microvilli and the accurate trafficking of glycoproteins to relevant membrane domains. Numerous transport pathways warrant the unique structural identity and protein/lipid composition of the brush border membrane. Annexin II (Ca(2+)-dependent lipid-binding protein) is an important component of one of the apical protein transport machineries, which involves detergent-resistant membranes and the actin cytoskeleton. Here, we investigate in intestinal Caco-2 cells the contribution of annexin II to the sorting and transport of brush border hydrolases and role in intestinal cell polarity. Downregulation of annexin II in Caco-2-A4 cell line results in a severe reduction of the levels of the brush border membrane resident enzyme sucrase isomaltase (SI) as well as structural components such as ezrin. This reduction is accompanied by a redistribution of these proteins to intracellular compartments and a striking morphological transition of Caco-2 cells to rudimentary epithelial cells that are characterized by an almost flat apical membrane with sparse and short microvilli. Concomitant with this alteration is the redistribution of the intermediate filament protein keratin 19 to the intracellular membranes in Caco-2-A4 cells. Interestingly, keratin 19 interacts with annexin II in wild type Caco-2 cells and this interaction occurs exclusively in lipid rafts. Our findings suggest a role for annexin II and K19 in differentiation and polarization of intestinal cells.
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Hein
authors.forename: Sonja
authors.initials: S
authors.lastname: Schmidt
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Zimmer
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
mesh_terms: D000199:Actins / Q000378:metabolism; D017306:Annexin A2 / Q000235:genetics / Q000502:physiology*; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000201:enzymology; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000201:enzymology; D007425:Intracellular Membranes / Q000378:metabolism; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D021381:Protein Transport; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D000199:Actins; D017306:Annexin A2; D003598:Cytoskeletal Proteins; D053539:Keratin-19; D013394:Sucrase-Isomaltase Complex; D000099149:Ezrin