Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts.
In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.
Georgakopoulos
A
A
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Marambaud
P
P
Efthimiopoulos
S
S
Shioi
J
J
Cui
W
W
Li
H C
HC
Schütte
M
M
Gordon
R
R
Holstein
G R
GR
Martinelli
G
G
Mehta
P
P
Friedrich
V L
VL
Robakis
N K
NK
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004285:Dogs; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D053764:Presenilin-1; D011817:Rabbits; D013569:Synapses / Q000378:metabolism*
D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1