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J. Cell Biol.,
Volume 140, Number 6, March 23, 1998 1475-1484
* Laboratory of Vascular Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and The two major cadherins of endothelial cells
are neural (N)-cadherin and vascular endothelial (VE)-
cadherin. Despite similar level of protein expression
only VE-cadherin is located at cell-cell contacts,
whereas N-cadherin is distributed over the whole cell membrane. Cotransfection of VE-cadherin and N-cadherin in CHO cells resulted in the same distribution as
that observed in endothelial cells indicating that the behavior of the two cadherins was not cell specific but related to their structural characteristics. Similar amounts
of II° Dipartimento di
Medicina Sperimentale e Patologia, Universitá di Roma La Sapienza, Rome, Italy
- and 
-catenins and plakoglobin were associated to
VE- and N-cadherins, whereas p120 was higher in the
VE-cadherin complex. The presence of VE-cadherin
did not affect N-cadherin homotypic adhesive properties or its capacity to localize at junctions when cotransfectants were cocultured with cells transfected
with N-cadherin only. To define the molecular domain
responsible for the VE-cadherin-dominant activity we
prepared a chimeric construct formed by VE-cadherin
extracellular region linked to N-cadherin intracellular
domain. The chimera lost the capacity to exclude N-cadherin from junctions indicating that the extracellular
domain of VE-cadherin alone is not sufficient for the
preferential localization of the molecule at the junctions. A truncated mutant of VE-cadherin retaining the
full extracellular domain and a short cytoplasmic tail
(Arg621-Pro702) lacking the catenin-binding region was
able to exclude N-cadherin from junctions. This indicates that the Arg621-Pro702 sequence in the VE-cadherin cytoplasmic tail is required for N-cadherin exclusion from junctions. Competition between cadherins for their clustering at intercellular junctions in the same
cell has never been described before. We speculate
that, in the endothelium, VE- and N-cadherin play different roles; whereas VE-cadherin mostly promotes the
homotypic interaction between endothelial cells, N-cadherin may be responsible for the anchorage of the endothelium to other surrounding cell types expressing
N-cadherin such as vascular smooth muscle cells or
pericytes.
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