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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
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.
Naim
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- -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 -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.
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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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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