First Author | Cai D | Year | 2006 |
Journal | Proc Natl Acad Sci U S A | Volume | 103 |
Issue | 6 | Pages | 1941-6 |
PubMed ID | 16449386 | Mgi Jnum | J:248239 |
Mgi Id | MGI:6092896 | Doi | 10.1073/pnas.0510708103 |
Citation | Cai D, et al. (2006) Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation. Proc Natl Acad Sci U S A 103(6):1941-6 |
abstractText | 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. |