Differential targeting of T- and N-cadherin in polarized epithelial cells.
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. NDeltacyt, 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-NDeltacyt, 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.
Koller
E
E
The Burnham Institute, La Jolla Cancer Research Center, La Jolla, California 92307, USA. ranscht@ljcrf.edu
Ranscht
B
B
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary; D004285:Dogs; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D018076:DNA, Complementary; C099972:H-cadherin; D009419:Nerve Tissue Proteins