MOLECULAR NEUROSCIENCEPresenilin 1 expression in yeast lowers secretion of the amyloid precursor proteinEvin, Geneviève1,3; Brocque, Darren Le1; Culvenor, Janetta G.1; Galatis, Denise1; Weidemann, Andreas2; Beyreuther, Konrad2; Masters, Colin L.1; Cappai, Roberto1Author Information 1Department of Pathology, The University of Melbourne, and Mental Health Research Institute, Parkville, Victoria 3052, Australia 2Center for Molecular Biology, ZMBH, University of Heidelberg, Heidelberg, D-69120, Germany 3Corresponding Author: Geneviève Evin Received 21 October 1999; accepted 26 November 1999 Acknowledgements: We thank Dr Carol Gray (SmithKline Beecham, Harlow, England) for providing mAb 1A9, Prof. Sam Gandy (New York University, Orangeburg, NY) for antibody 369, Monna Ayad for 95/23, and Fiona Cochrane and Robyn Sharples for technical help. This work is supported by grants from the NH-MRC (970315) and the Deutsche Forschungsgemeinschaft and the Bundesministerium für Forschung und Technologie. NeuroReport: February 7, 2000 - Volume 11 - Issue 2 - p 405-408 Buy Abstract Presenilin (PS) mutations are associated with early-onset Alzheimer's disease and PS proteins are involved with β-secretase cleavage of the amyloid precursor protein, APP. We have shown previously that α-, β and γ-secretase cleavages of APP are conserved in Pichia pastoris. Here, we report coexpression of APP and PS1 in P. pastoris and show by immunoelectron microscopy colocalization of these two proteins in expanded endoplasmic reticulum. Western blot analysis indicates a drastic reduction of both α and β-secretase products. A relative increase in β-secretase product derived from immature APP is also observed, pointing to a β-secretase activity of P. pastoris associated with the early secretory pathway. © 2000 Lippincott Williams & Wilkins, Inc.