Identifying the beta-site amyloid precursor protein cleaving enzyme 1 interactome through the proximity-dependent biotin identification assay

Jennie L. Gabriel, Michele Tinti, William Fuller, Michael L. J. Ashford (Lead / Corresponding author)

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Abstract

Beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is a key drug target against Alzheimer's Disease however, due to its promiscuous proteolytic activity, little is known about its physiological functions. Previous studies have analysed BACE1 cleavage products to examine BACE1 interactions and determine substrates, but these studies cannot establish non-enzymatic (and potentially functional) associations. This study used the biotin identification proximity assay to establish the BACE1 interactome in healthy neuronal cells and identified interactions involved in BACE1 trafficking, post-translational modification and substrates. Furthermore, this method has identified a putative novel role for BACE1 in sex hormone signalling and haem regulation through interaction with the progesterone receptor membrane component 2 (PGRC2). Data are available via ProteomeXchange with identifier PXD021464.

Original languageEnglish
Article number136302
Number of pages7
JournalNeuroscience Letters
Volume767
Early online date25 Oct 2021
DOIs
Publication statusPublished - 10 Jan 2022

Keywords

  • Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)
  • Proximity-dependent biotin identification (BioID) assay
  • Interactomics
  • Alzheimer’s disease
  • Progesterone receptor membrane component 2 (PGRC2)
  • Alzheimer's disease

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