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

doi:10.1016/j.neulet.2021.136302

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)

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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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 language	English
Article number	136302
Number of pages	7
Journal	Neuroscience Letters
Volume	767
Early online date	25 Oct 2021
DOIs	https://doi.org/10.1016/j.neulet.2021.136302
Publication status	Published - 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

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neulet.2021.136302Licence: CC BY

Final published versionFinal published version, 1.2 MBLicence: CC BY

Cite this

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

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.",

keywords = "Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), Proximity-dependent biotin identification (BioID) assay, Interactomics, Alzheimer{\textquoteright}s disease, Progesterone receptor membrane component 2 (PGRC2), Alzheimer's disease",

author = "Gabriel, {Jennie L.} and Michele Tinti and William Fuller and Ashford, {Michael L. J.}",

note = "Copyright {\textcopyright} 2021. Published by Elsevier B.V. This work was supported by Alzheimer{\textquoteright}s Society (AS DTC-2014-017) and Alzheimer{\textquoteright}s Research UK. J.G. was supported by an Alzheimer{\textquoteright}s Society Doctoral Training PhD studentship. The contributions of M.Tinti were supported by a Wellcome Trust Investigator Award to Mike A J Ferguson (101842/Z/13/Z).",

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doi = "10.1016/j.neulet.2021.136302",

language = "English",

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journal = "Neuroscience Letters",

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AU - Gabriel, Jennie L.

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AU - Fuller, William

AU - Ashford, Michael L. J.

N1 - Copyright © 2021. Published by Elsevier B.V. This work was supported by Alzheimer’s Society (AS DTC-2014-017) and Alzheimer’s Research UK. J.G. was supported by an Alzheimer’s Society Doctoral Training PhD studentship. The contributions of M.Tinti were supported by a Wellcome Trust Investigator Award to Mike A J Ferguson (101842/Z/13/Z).

PY - 2022/1/10

Y1 - 2022/1/10

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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Small Molecules Activating Nrf2 as a Therapeutic Approach to Prevent Cardiac Ischemia-reperfusion Injury (joint with University of Glasgow)

Palmitoylation of the L-Type Ca Channel Pore-Forming Subunit (joint with University of Bristol)

Metabolic and Vascular Contributors to Dementia (Joint with Universities of Edinburgh, Aberdeen and St Andrews)

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

Small Molecules Activating Nrf2 as a Therapeutic Approach to Prevent Cardiac Ischemia-reperfusion Injury (joint with University of Glasgow)

Palmitoylation of the L-Type Ca Channel Pore-Forming Subunit (joint with University of Bristol)

Metabolic and Vascular Contributors to Dementia (Joint with Universities of Edinburgh, Aberdeen and St Andrews)

Cite this