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PMID: 11953314 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions.

The EMBO journal ·Vol. 21 ·No. 8 ·2002-04-15 ·Pages 1948-56

Marambaud P, Shioi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, Baki L, Wen P, Efthimiopoulos S, Shao Z, Wisniewski T, Robakis NK

Abstract

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 disassembly 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.

MeSH Terms
Adherens Junctions Amino Acid Sequence Amyloid Precursor Protein Secretases Animals Aspartic Acid Endopeptidases Binding Sites Cadherins/genetics,metabolism Endopeptidases/metabolism Humans Intracellular Fluid Matrix Metalloproteinases/metabolism Membrane Proteins/genetics,metabolism Mice Mice, Knockout Molecular Sequence Data Presenilin-1 Protein Processing, Post-Translational
Chemicals
Cadherins Membrane Proteins PSEN1 protein, human Presenilin-1 Amyloid Precursor Protein Secretases Endopeptidases Aspartic Acid Endopeptidases BACE1 protein, human Bace1 protein, mouse Matrix Metalloproteinases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Marambaud Philippe
Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
Shioi Junichi
Serban Geo
Georgakopoulos Anastasios
Sarner Shula
Nagy Vanja
Baki Lia
Wen Paul
Efthimiopoulos Spiros
Shao Zhiping
Wisniewski Thomas
Robakis Nikolaos K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/21.8.1948
Published
2002-04-15
Pages
1948-56
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125968
Subset
IM
Grants
NIA NIH HHS · AG-15408 · United States
NIA NIH HHS · AG-08200 · United States
NIA NIH HHS · AG-17926 · United States
NIA NIH HHS · R01 AG008200 · United States
NIA NIH HHS · R37 AG017926 · United States
NIA NIH HHS · P50 AG005138 · United States
NIA NIH HHS · R01 AG015408 · United States
NIA NIH HHS · AG-05138 · United States
NIA NIH HHS · R01 AG017926 · United States
External Links
PubMed source DOI: 10.1093/emboj/21.8.1948 PMC Full Text View journal details
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