Phosphorylation of cellular adaptor GULP1 regulates Alzheimer’s disease amyloid precursor protein processing
Refereed conference paper presented and published in conference proceedings

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AbstractAmyloid-β (Aβ) is derived from the proteolytic processing of amyloid precursor protein (APP), and the deposition of extracellular Aβ to form amyloid plaques is a pathological hallmark of Alzheimer’s disease (AD). Engulfment adaptor PTB domain containing 1 (GULP1) is a molecular adaptor that has been shown to interact with APP to alter Aβ production. Therefore, the modulation of GULP1-APP interaction may be an alternative approach to reducing Aβ. However, the mechanisms that regulate GULP1-APP binding remain elusive. As GULP1 is a phosphoprotein, and because phosphorylation is a common mechanism that regulates protein interaction, we anticipated that GULP1 phosphorylation would influence GULP1-APP interaction and thereby Aβ production. In fact, we have found that phosphorylation of a residue within the GULP1 PTB domain reduces GULP1-APP interaction and suppresses the stimulatory effect of GULP1 on APP processing. Moreover, the kinase for the residue has been identified. Overexpression of the kinase reduces both GULP1-APP interaction and GULP1-mediated Aβ generation. Additionally, our X-ray crystal structure of GULP1 PTB-APP intracellular domain (AICD) peptide has revealed that the GULP1 phosphorylatable residue is not located at the GULP1-AICD binding interface. Together, we have identified a mechanism for regulating GULP1-mediated APP processing.
All Author(s) ListKF LAU, JCK NGO, DDL CHAU
Name of ConferenceNeuroscience 2019
Start Date of Conference19/10/2019
End Date of Conference23/10/2019
Place of ConferenceChicago
Country/Region of ConferenceUnited States of America
LanguagesEnglish-United States
KeywordsAmyloid-β, amyloid precursor protein, GULP1

Last updated on 2020-27-05 at 12:51