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Neuron. 1996 Nov;17(5):1015-21.

Membrane topology of the C. elegans SEL-12 presenilin.

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Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.


Mutant presenilins cause Alzheimer's disease. Presenilins have multiple hydrophobic regions that could theoretically span a membrane, and a knowledge of the membrane topology is crucial for deducing the mechanism of presenilin function. By analyzing the activity of beta-galactosidase hybrid proteins expressed in C. elegans, we show that the C. elegans SEL-12 presenilin has eight transmembrane domains and that there is a cleavage site after the sixth transmembrane domain. We examine the presenilin sequence in view of the predicted topology and discuss possible mechanisms for presenilin function.

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