Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin.
Missense substitutions in the presenilin 1 (PS1) and presenilin 2 (PS2) proteins are associated with early-onset familial Alzheimer's disease. We have used yeast-two-hybrid and coimmunoprecipitation methods to show that the large cytoplasmic loop domains of PS1 and PS2 interact specifically with three members of the armadillo protein family, including beta-catenin, p0071, and a novel neuronal-specific armadillo protein--neural plakophilin-related armadillo protein (NPRAP). The PS1:NPRAP interaction occurs between the arm repeats of NPRAP and residues 372-399 at the C-terminal end of the large cytoplasmic loop of PS1. The latter residues contain a single arm-like domain and are highly conserved in the presenilins, suggesting that they form a functional armadillo protein binding site for the presenilins.
Centre for Research in Neurodegenerative Diseases, Department of Medicine (Neurology), University of Toronto, and Toronto Hospital, Ontario, Canada.
G
G
Levesque
G
G
Yu
M
M
Nishimura
D M
DM
Zhang
L
L
Levesque
H
H
Yu
D
D
Xu
Y
Y
Liang
E
E
Rogaeva
M
M
Ikeda
M
M
Duthie
N
N
Murgolo
L
L
Wang
P
P
VanderVere
M L
ML
Bayne
C D
CD
Strader
J M
JM
Rommens
P E
PE
Fraser
P
P
St George-Hyslop
D000544:Alzheimer Disease / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins; D051191:Plakophilins; D011233:Precipitin Tests; D053764:Presenilin-1; D053766:Presenilin-2; D011485:Protein Binding; D015534:Trans-Activators; D014162:Transfection; D051176:beta Catenin; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C105677:PKP4 protein, human; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010750:Phosphoproteins; D051191:Plakophilins; D053764:Presenilin-1; D053766:Presenilin-2; D015534:Trans-Activators; D051176:beta Catenin; D000095002:Delta Catenin