Work

Correction: Differential Regulation of Amyloid Precursor Protein/Presenilin 1 Interaction during Ab40/42 Production Detected Using Fusion Constructs

Year: 2012

Type: erratum

Abstract: Beta amyloid peptides (Ab) play a key role in the pathogenesis of Alzheimer disease (AD).Presenilins (PS) function as the catalytic subunits of c-secretase, the enzyme that releases Ab from ectodomain cleaved amyloid precursor protein (APP) by intramembrane proteolysis.Familial Alzheimer disease (FAD)-linked PSEN mutations alter APP processing in a manner that increases the relative abundance of longer Ab42 peptides to that of Ab40 peptides.The mechanisms by which Ab40 and Ab42 peptides are produced in a ratio of ten to one by wild type presenilin (PS) and by which Ab42 is overproduced by FAD-linked PS variants are not completely understood.We generated chimeras of the amyloid precursor protein C-terminal fragment (C99) and PS to address this issue.We found a chimeric protein where C99 is fused to the PS1 N-terminus undergoes in cis processing to produce Ab and that a fusion protein harboring FAD-linked PS1 mutations overproduced Ab42.To change the molecular interactions within the C99-PS1 fusion protein, we made sequential deletions of the junction between C99 and PS1.We found differential effects of deletion in C99-PS1 on Ab40 and 42 production.Deletion of the junction between APP CTF and PS1 in the fusion protein decreased Ab40, while it did not decrease Ab42 production in the presence or absence of FAD-linked PS1 mutation.These results are consistent with the idea that the APP/PS interaction is differentially regulated during Ab40 and 42 production.

Source: PLoS ONE

DOI: 10.1371/annotation/5cac3524-f2a4-4997-ba21-a5f1d8551f59