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Updated: Jun 18, 2025
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
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The cellular adaptor GULP1 interacts with ATG14 to potentiate autophagy and APP processing
Dennis Dik-Long Chau1, Zhicheng Yu1, Wai Wa Ray Chan1
1School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Hong Kong SAR, China.
Cellular and Molecular Life Sciences : CMLS
|July 30, 2024
Summary
Engulfment adaptor phosphotyrosine-binding domain-containing protein 1 (GULP1) enhances autophagy by targeting autophagy-related 14 (ATG14) to the endoplasmic reticulum. This process stimulates amyloid precursor protein (APP) processing, offering potential therapeutic insights for neurodegenerative diseases like Alzheimer's disease.
Area of Science:
- Cell Biology
- Neuroscience
- Molecular Biology
Background:
- Autophagy is a crucial cellular process for removing damaged components, and its dysregulation is linked to neurodegenerative diseases such as Alzheimer's disease (AD).
- Engulfment adaptor phosphotyrosine-binding domain-containing protein 1 (GULP1) is known to interact with amyloid precursor protein (APP) and influence amyloid-beta production.
- Emerging evidence suggests a role for GULP1 in the regulation of autophagy.
Purpose of the Study:
- To elucidate the role of GULP1 in autophagy and its connection to Alzheimer's disease pathology.
- To investigate the molecular mechanism by which GULP1 influences autophagy and amyloid precursor protein (APP) processing.
Main Methods:
- Investigated the interaction between GULP1 and autophagy-related 14 (ATG14).
- Assessed the effect of GULP1 on class III phosphatidylinositol 3-kinase complex 1 (PI3KC3-C1) activity.
- Utilized GULP1 mutations to disrupt GULP1-ATG14 interaction and analyzed APP processing in cells expressing GULP1 and ATG14.
Main Results:
- GULP1 interacts with ATG14, a key regulator of autophagosome formation, and potentiates its activity by modulating PI3KC3-C1.
- GULP1 facilitates the targeting of ATG14 to the endoplasmic reticulum (ER), leading to increased autophagic vacuoles (AVs) containing ATG14 and APP.
- APP processing is significantly enhanced in cells co-expressing GULP1 and ATG14, indicating GULP1's role in promoting APP entry into AVs.
Conclusions:
- GULP1 plays a novel role in stimulating autophagy by enhancing ATG14 targeting to the ER.
- This GULP1-mediated autophagy stimulation consequently enhances amyloid precursor protein (APP) processing.
- Understanding this pathway may offer new therapeutic avenues for Alzheimer's disease and other neurodegenerative disorders.
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