期刊
EMBO JOURNAL
卷 21, 期 8, 页码 1948-1956出版社
OXFORD UNIV PRESS
DOI: 10.1093/emboj/21.8.1948
关键词
Alzheimer's disease; beta-catenin; E-cadherin; presenilin-1/gamma-secretase
资金
- NIA NIH HHS [AG-15408, AG-08200, AG-17926, R01 AG008200, R37 AG017926, P50 AG005138, R01 AG015408, AG-05138, R01 AG017926] Funding Source: Medline
E-cadherin controls a wide array of cellular behaviors including cell-cell adhesion, differentiation and tissue development. Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, controls a gamma-secretase-like cleavage of E-cadherin. This cleavage Is stimulated by apoptosis or calcium influx and occurs between human E-cadherin residues Leu731 and Arg732 at the membrane-cytoplasm interface. The PS1/gamma-secretase system cleaves both the full-length E-cadherin and a transmembrane C-terminal fragment, derived from a metalloproteinase cleavage after the E-cadherin ectodomain residue Pro700. The PS1/gamma-secretase cleavage dissociates E-cadherins, beta-catenin and alpha-catenin from the cytoskeleton, thus promoting dis-assembly of the E-cadherin-catenin adhesion complex. Furthermore, this cleavage releases the cytoplasmic E-cadherin to the cytosol and increases the levels of soluble beta- and alpha-catenins. Thus, the PS1/gamma-secretase system stimulates disassembly of the E-cadherin-catenin complex and increases the cytosolic pool of beta-catenin, a key regulator of the Wnt signaling pathway.
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