Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein. Academic Article uri icon

Overview

abstract

  • Presenilins (PS1/PS2) play a critical role in proteolysis of beta-amyloid precursor protein (beta APP) to generate beta-amyloid, a peptide important in the pathogenesis of Alzheimer's disease. Nevertheless, several regulatory functions of PS1 have also been reported. Here we demonstrate, in neuroblastoma cells, that PS1 regulates the biogenesis of beta APP-containing vesicles from the trans-Golgi network and the endoplasmic reticulum. PS1 deficiency or the expression of loss-of-function variants leads to robust vesicle formation, concomitant with increased maturation and/or cell surface accumulation of beta APP. In contrast, release of vesicles containing beta APP is impaired in familial Alzheimer's disease (FAD)-linked PS1 mutant cells, resulting in reduced beta APP delivery to the cell surface. Moreover, diminution of surface beta APP is profound at axonal terminals in neurons expressing a PS1 FAD variant. These results suggest that PS1 regulation of beta APP trafficking may represent an alternative mechanism by which FAD-linked PS1 variants modulate beta APP processing.

publication date

  • November 14, 2002

Research

keywords

  • Amyloid beta-Protein Precursor
  • Golgi Apparatus
  • Membrane Proteins
  • trans-Golgi Network

Identity

Scopus Document Identifier

  • 0037474287

Digital Object Identifier (DOI)

  • 10.1074/jbc.M209065200

PubMed ID

  • 12435726

Additional Document Info

volume

  • 278

issue

  • 5