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Vol. 9, Issue 6, 1589-1601, June 1998
-Catenin and Plakoglobin and Shedding of
VE-Cadherin during Endothelial Apoptosis: Evidence for a Role for
Caspases and Metalloproteinases
Department of Pathology, University of Washington School of
Medicine, Seattle, Washington 98195-7570
Growth factor deprivation of endothelial cells induces apoptosis,
which is characterized by membrane blebbing, cell rounding, and
subsequent loss of cell-matrix and cell-cell contacts. In this study,
we show that initiation of endothelial apoptosis correlates with
cleavage and disassembly of intracellular and extracellular components
of adherens junctions. 
-Catenin and plakoglobin, which form
intracellular links between vascular endothelial cadherin (VE-cadherin)
and actin-binding 
-catenin in adherens junctions, are cleaved in
apoptotic cells. In vitro incubations of cell lysates and
immunoprecipitates with recombinant caspases indicate that CPP32 and
Mch2 are involved, possibly by initiating proteolytic processing.
Cleaved -catenin from lysates of apoptotic cells does not bind to
endogenous -catenin, whereas plakoglobin retains its binding
capacity. The extracellular portion of the adherens junctions is also
altered during apoptosis because VE-cadherin, which mediates
endothelial cell-cell interactions, dramatically decreases on the
surface of cells. An extracellular fragment of VE-cadherin can be
detected in the conditioned medium, and this "shedding" of
VE-cadherin can be blocked by an inhibitor of metalloproteinases. Thus,
cleavage of -catenin and plakoglobin and shedding of VE-cadherin may
act in concert to disrupt structural and signaling properties of
adherens junctions and may actively interrupt extracellular signals
required for endothelial cell survival.
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