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Originally published In Press as doi:10.1074/jbc.M109357200 on December 28, 2001

J. Biol. Chem., Vol. 277, Issue 12, 10683-10690, March 22, 2002
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Intestinal Dipeptidyl Peptidase IV Is Efficiently Sorted to the Apical Membrane through the Concerted Action of N- and O-Glycans as Well as Association with Lipid Microdomains*

Marwan Alfalah, Ralf Jacob, and Hassan Y. NaimDagger

From the Department of Physiological Chemistry, School of Veterinary Medicine Hannover, Hannover D-30559, Germany

The apical sorting of human intestinal dipeptidyl peptidase IV (DPPIV) occurs through complex N-linked and O-linked carbohydrates. Inhibition of O-linked glycosylation by benzyl-N-acetyl-alpha -D-galactosaminide affects significantly the sorting behavior of DPPIV in intestinal Caco-2 and HT-29 cells. However, random delivery to the apical and basolateral membranes and hence a more drastic effect on the sorting of DPPIV in both cell types is only observed when, in addition to O-glycans, the processing of N-glycans is affected by swainsonine, an inhibitor of mannosidase II. Together the data indicate that both types of glycosylation are critical components of the apical sorting signal of DPPIV. The sorting mechanism of DPPIV implicates its association with detergent-insoluble membrane microdomains containing cholesterol and sphingolipids, whereas an efficient association largely depends on the presence of a fully complex N- and O-linked glycosylated DPPIV. Interestingly, cholesterol is a more critical component in this context than sphingolipids, because cholesterol depletion by beta -cyclodextrin affects the detergent solubility and the sorting behavior of DPPIV more strongly than fumonisin, an inhibitor of sphingolipid synthesis.


* This work was supported by Grant Na 331/1-2 from the Deutsche Forschungsgemeinschaft, Bonn, Germany (to H. Y. N.), and the Sonderforschungsbereich 280.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom all correspondence should be addressed: Dept. of Physiological Chemistry, School of Veterinary Medicine, Hannover, Bünteweg 17, D-30559 Hannover, Germany. Tel.: 49-511-9538780; Fax: 49-511- 9538585; E-mail: Hassan.Naim@tiho-hannover.de.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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