The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains β-catenin

G. Yu, F. Chen, G. Levesque, M. Nishimura, D. M. Zhang, L. Levesque, E. Rogaeva, D. Xu, Y. Liang, M. Duthie, P. H. St George-Hyslop, P. E. Fraser

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Abstract

The presenilin (PS) genes associated with Alzheimer disease encode polytopic transmembrane proteins which undergo physiologic endoproteolytic cleavage to generate stable NH2- and COOH-terminal fragments (NTF or CTF) which co-localize in intracellular membranes, but are tightly regulated in their stoichiometry and abundance. We have used linear glycerol velocity and discontinuous sucrose gradient analysis to investigate the distribution and native conformation of PSI and PS2 during this regulated processing in cultured cells and in brain. The PSI NTF and CTF co-localize in the endoplasmic reticulum (ER) and in the Golgi apparatus, where they are components of a ~250-kDa complex. This complex also contains β-catenin but not β-amyloid precursor protein (APP). In contrast, the PS1 holoprotein precursor is predominantly localized to the rough ER and smooth ER, where it is a component of a ~180-kDa native complex. PS2 forms similar but independent complexes. Restricted incorporation of the presenilin NTF and CTF along with a potentially functional ligand (β-catenin) into a multimeric complex in the ER and Golgi apparatus may provide an explanation for the regulated accumulation of the NTF and CTF.

Original languageEnglish (US)
Pages (from-to)16470-16475
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number26
DOIs
StatePublished - Jun 26 1998

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yu, G., Chen, F., Levesque, G., Nishimura, M., Zhang, D. M., Levesque, L., Rogaeva, E., Xu, D., Liang, Y., Duthie, M., St George-Hyslop, P. H., & Fraser, P. E. (1998). The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains β-catenin. Journal of Biological Chemistry, 273(26), 16470-16475. https://doi.org/10.1074/jbc.273.26.16470