Subcellular distribution and turnover of presenilins in transfected cells

Jimin Zhang, David E. Kang, Weiming Xia, Masayasu Okochi, Hiroshi Mori, Dennis J. Selkoe, Edward H. Koo

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

The mechanisms by which mutations in presenilin-1 (PS1) and presenilin- 2 (PS2) result in the Alzheimer's disease phenotype are unclear. Full-length PS1 and PS2 are each processed into stable proteolytic fragments after their biosynthesis in transfected cells. PS1 and PS2 have been localized by immunocytochemistry to the endoplasmic reticulum (ER) and Golgi compartments, but previous studies could not differentiate between the full-length presenilin proteins and their fragments. We carried out subcellular fractionation of cells stably transfected with PS1 or PS2 to determine the localization of full-length presenilins and their fragments. Full-length PS1 and PS2 were principally distributed in ER fractions, whereas the N- and C- terminal fragments were localized predominantly to the Golgi fractions. In cells expressing the PS1 mutant lacking exon 9 (ΔE9), we observed only full- length molecules that were present in the ER and Golgi fractions. The turnover rate was considerably slower for the ΔE9 holoprotein, apparently due to decreased degradation within the ER. Our results suggest that full- length presenilin proteins are primarily ER resident molecules and undergo endoproteolysis within the ER. The fragments are subsequently transported to the Golgi compartment, where their turnover rate is much slower than that of the full-length presenilin in the ER.

Original languageEnglish (US)
Pages (from-to)12436-12442
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number20
DOIs
StatePublished - May 15 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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