Zhang D M, Levitan D, Yu G, Nishimura M, Chen F, Tandon A, Kawarai T, Arawaka S, Supala A, Song Y Q, Rogaeva E, Liang Y, Holmes E, Milman P, Sato C, Zhang L, St George-Hyslop P
Centre for Research in Neurodegenerative Diseases, Department of Medicine (Neurology), The University Health Network, University of Toronto, Ontario, Canada.
Neuroreport. 2000 Sep 28;11(14):3227-30. doi: 10.1097/00001756-200009280-00035.
The presenilin proteins are involved in the proteolytic processing of transmembrane proteins such as Notch/lin-12 and the beta-amyloid precursor protein (betaAPP). Mutation of a conserved cysteine (Cys60Ser) in the C. elegans presenilin sel-12 has a loss-of-function effect on Notch/lin-12 processing similar to that of null mutations in sel-12. In contrast, in mammalian cells, most missense mutations increase gamma-secretase cleavage of betaAPP. We report here that mutation of this conserved cysteine (Cys92Ser) in human presenilin 1 confers a loss-of-function effect in C. elegans, but causes increased A beta42 secretion in mammalian cells. These data suggest that the role of presenilins in Notch/lin-12 signalling and betaAPP processing are either separately regulated activities or independent activities of the presenilins.
