کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10750711 | 1050302 | 2015 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Threonine 576 residue of amyloid-β precursor protein regulates its trafficking and processing
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Deposition of amyloid-β (Aβ) in the brain is the main culprit of Alzheimer's disease (AD). Aβ is derived from sequential proteolytic cleavage of amyloid-β precursor protein (APP). Newly synthesized APP is transported from endoplasmic reticulum to the plasma membrane via trans-Golgi network (TGN) after post-translational modification including N- and O-glycosylation. APP is internalized through clathrin-dependent endocytosis from the plasma membrane to the early endosomes. In this study, we investigated the regulation of APP trafficking and processing by mutating three threonine residues known as O-glycosylation sites. We separately mutated three threonine residues of APP695 into alanines (T291A, T292A, and T576A) and expressed them in HeLa cells. Among these APP mutants, only T576A mutant showed reduced cell surface levels, indicating this residue regulates its trafficking. We also confirmed that trafficking from TGN to the plasma membrane was decreased in T576A mutant. Consistent with these observations, T576A mutant accumulated in the early endosomes, and the secreted Aβ level was increased. Thus, these results indicate that threonine 576 residue of APP regulates its trafficking and processing.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 467, Issue 4, 27 November 2015, Pages 955-960
Journal: Biochemical and Biophysical Research Communications - Volume 467, Issue 4, 27 November 2015, Pages 955-960
نویسندگان
Yoon Sun Chun, Oh-Hoon Kwon, Hyun Geun Oh, Tae-Wan Kim, Laura Beth McIntire, Myoung Kyu Park, Sungkwon Chung,