Article
- The EMBO Journal (2002) 21, 1948 - 1956
- doi:10.1093/emboj/21.8.1948
Subject Category:
A presenilin-1/
-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions
Philippe Marambaud1, Junichi Shioi1, Geo Serban1, Anastasios Georgakopoulos1, Shula Sarner1, Vanja Nagy1, Lia Baki1, Paul Wen1, Spiros Efthimiopoulos1, Zhiping Shao1, Thomas Wisniewski2 and Nikolaos K. Robakis1
- Department of Psychiatry and Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York University, New York, NY 10029 USA
- Departments of Neurology and Pathology, New York University Medical Center, New York, NY 10016, USA
Correspondence to:
Nikolaos K. Robakis, E-mail: nikos.robakis@mssm.edu
Received 11 December 2001; Accepted 25 February 2002; Revised 7 February 2002
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 
-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/-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/-secretase cleavage dissociates E-cadherins, 
-catenin and 
-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 - and -catenins. Thus, the PS1/-secretase system stimulates disassembly of the E-cadherin– catenin complex and increases the cytosolic pool of -catenin, a key regulator of the Wnt signaling pathway.
Keywords:
- Alzheimer's disease,
- -catenin,
- E-cadherin,
- presenilin-1,
- -secretase
