Formation of stable complexes between two Alzheimer's disease gene products: presenilin-2 and beta-amyloid precursor protein.
Mutations in the presenilin genes are associated with early onset familial Alzheimer's disease and lead to increased accumulation of beta A4 peptide, the proteolytic product of the amyloid precursor protein (APP). To test whether presenilins interfere with APP metabolism, presenilin-2 (PS2) was coexpressed with APP in mammalian cells. Analysis of PS2 immunoprecipitates revealed that a fraction of APP was associated with the PS2 immunocomplexes. This non-covalent association was specific for the APP family of proteins and restricted to immature forms, occurring probably during transit through the endoplasmic reticulum. Additionally, coexpression with PS2 resulted in a decrease of APP secretion, suggesting a direct participation of presenilins in the intracellular sorting, trafficking and processing of APP molecules.
Weidemann
A
A
Zentrum für Molekulare Biologie Heidelberg, ZMBH, Germany.
Paliga
K
K
Dürrwang
U
U
Czech
C
C
Evin
G
G
Masters
C L
CL
Beyreuther
K
K
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D053766:Presenilin-2; D011485:Protein Binding; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2