Identifying the beta-site amyloid precursor protein cleaving enzyme 1 interactome through the proximity-dependent biotin identification assay. (10th January 2022)

• Record Type: Journal Article
• Authors: Gabriel, Jennie L.; Tinti, Michele; Fuller, William; Ashford, Michael L.J.
• Is Part Of: Neuroscience letters. Volume 767(2022)
• Publication Date: 2022-01-10
• Subjects: BACE1 Beta-site APP cleaving enzyme 1 -- APP amyloid precursor protein -- PGRC2 progesterone receptor membrane component 2 -- Aβ amyloid beta; 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); Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.136302
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Biotin identification proximity assay used to determine BACE1 interactome. Insight into BACE1 trafficking and protein interactions independent of proteolysis. Identified progesterone receptor component 2 as a novel BACE1 protein partner. 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.