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Volume 271, Number 47, Issue of November 22, 1996 pp. 30061-30067
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Targeting of T- and N-cadherin in Polarized Epithelial Cells

(Received for publication, June 19, 1996, and in revised form, August 19, 1996)

Erich Koller and Barbara Ranscht

From The Burnham Institute, La Jolla Cancer Research Center, La Jolla, California 92307

To test whether glycosyl phosphatidylinositol-linked T-cadherin is a component of cell junctions like classical cadherins, we have examined its distribution and targeting in polarized epithelial cells. In vivo, T-cadherin was detected on the apical cell surface of the chick intestinal epithelium. In cultures of transfected Madin-Darby canine kidney cells, T-cadherin was also expressed apically, whereas classical N-cadherin resided basolaterally. Both cadherins were directly targeted to their respective membrane domains. Mutant proteins were expressed in Madin-Darby canine kidney cells to identify the regions responsible for differential cadherin localization. NDelta cyt, an N-cadherin cytoplasmic domain deletion mutant, was stably distributed basolaterally. This mutant was transported to both the apical and basolateral membrane compartments, followed by preferential removal from the apical surface. T-NDelta cyt, a T-cadherin mutant with the N-cadherin cytoplasmic domain deletion, was localized basolaterally, whereas N-TGPI, a GPI-anchored N-cadherin mutant, resided at the apical domain. The T-cadherin carboxyl-terminal 76 amino acids contain the apical targeting signal and include the signal for GPI anchor attachment. Basolateral localization of N-cadherin is achieved through targeting signals in the cytoplasmic domain. Thus, GPI-linked T-cadherin is not a component of cell junctions, consistent with a function as a recognition rather than a cell adhesion molecule.


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