Presenilin-1 interacts directly with the beta-site amyloid protein precursor cleaving enzyme (BACE1).
A neuropathological hallmark of Alzheimer's disease is the presence of amyloid plaques. The major constituent of these plaques, occurring largely in brain areas important for memory and cognition, is the 40-42 amyloid residues (Abeta). Abeta is derived from the amyloid protein precursor after cleavage by the recently identified beta-secretase (BACE1) and the putative gamma-secretase complex containing presenilin 1 (PS1). In an attempt to develop a functional secretase enzymatic assay in yeast we demonstrate a direct binding between BACE1 and PS1. This interaction was confirmed in vivo using coimmunoprecipitation and colocalization studies in human cultured cells. Our results show that PS1 preferably binds immature BACE1, thus possibly acting as a functional regulator of BACE1 maturation and/or activity.
Hébert
Sébastien S
SS
Molecular and Human Genetics Unit, CHUQ-Pavillon St-François d'Assise, 10 rue de 1' Espinay, G1L 3L5, Québec, Canada.
Bourdages
Valérie
V
Godin
Chantal
C
Ferland
Mélissa
M
Carreau
Madeleine
M
Lévesque
Georges
G
D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D010450:Endopeptidases; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D053764:Presenilin-1; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae; D014162:Transfection; D020798:Two-Hybrid System Techniques
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011994:Recombinant Proteins; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human