Abnormal gel-electrophoretic behavior of presenilin 1 and it's fragment

• Published in: Biochemical and biophysical research communications 1996-09, Vol.226 (2), p.536-541
• Main Authors: Yamamoto, A, Sahara, N, Usami, M, Okochi, M, Kondo, T, Kametani, F, Tanaka, K, Yahagi, Y, Shirasawa, T, Itoyama, Y, Mori, H
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Animals; Cell Line; DNA, Complementary; Electrophoresis, Polyacrylamide Gel; Hot Temperature; Humans; Membrane Proteins - chemistry; Membrane Proteins - genetics; Molecular Weight; Peptide Fragments - chemistry; Point Mutation; Presenilin-1; Protein Binding; Transfection
• ISSN: 0006-291X
• DOI: 10.1006/bbrc.1996.1390

Presenilin 1 (PS-1) is the main causal gene of familial Alzheimer's disease. In this report, we describe the abnormal behavior of PS-1 in gel electrophoresis in the presence of SDS. Freshly in vitro synthesized PS-1 was identified as a single molecule with the molecular size of 43,000 on SDS gels but was found to disappear after incubation at 37 degrees C for 24 hr due to the formation of aggregates. Intermediate aggregates with M(r) 74,000 and 100,000 were formed before the final aggregate which was retained at the top of the gel. Thus the amount of 43,000-protein species of PS-1 was found to decrease on gels with a concomitant increase in the amount of 74,000/100,000 proteins. Similar abnormality was seen in PS-1 expressed in COS cells transfected with PS-1 cDNA. Moreover, cellular PS-1 was strongly suggested to be cleaved into the fragments with M(r) approximately 20,000 in COS and CHO cells. Fragmentation of cellular PS-1 was not affected by the missense point mutation of Ala260Val on PS-1 which was identified in a pedigree with familial Alzheimer's disease.