Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 16449386.
- Also identified by PMC identifier 1413665.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Presenilin (PS1/PS2) is a major component of gamma-secretase, the activity that mediates proteolysis of beta-amyloid precursor protein to generate beta-amyloid (Abeta). Here we demonstrate that PS1, through its loop region, binds to phospholipase D1 (PLD1), thereby recruiting it to the Golgi/trans-Golgi network. Overexpression of wild-type PLD1 reduces Abeta generation. Conversely, down-regulation of endogenous PLD1 by small hairpin RNA elevates Abeta production. The Abeta-lowering effect of PLD1 is independent of its ability to promote vesicular budding of beta-amyloid precursor protein. The data indicate that overexpression of PLD1 decreases, and down-regulation of PLD1 increases, the catalytic activity, and the association of the subunits, of gamma-secretase.
Medical subject headings
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Membrane Proteins
- Phospholipase D
- Protein Processing, Post-Translational