Effects of PS1 deficiency on membrane protein trafficking in neurons

Neuron. 1998 Nov;21(5):1213-21. doi: 10.1016/s0896-6273(00)80637-6.


We have examined the trafficking and metabolism of the beta-amyloid precursor protein (APP), an APP homolog (APLP1), and TrkB in neurons that lack PS1. We report that PS1-deficient neurons fail to secrete Abeta, and that the rate of appearance of soluble APP derivatives in the conditioned medium is increased. Remarkably, carboxyl-terminal fragments (CTFs) derived from APP and APLP1 accumulate in PS1-deficient neurons. Hence, PS1 plays a role in promoting intramembrane cleavage and/or degradation of membrane-bound CTFs. Moreover, the maturation of TrkB and BDNF-inducible TrkB autophosphorylation is severely compromised in neurons lacking PS1. We conclude that PS1 plays an essential role in modulating trafficking and metabolism of a selected set of membrane and secretory proteins in neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Fetus
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / metabolism*
  • Presenilin-1


  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • Presenilin-1