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Publication : Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation.

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.
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