Regulation of amyloid precursor protein processing by its KFERQ motif

BMB Reports

Ji-Seon Park^1,2,3,4¹  Seung-Yong Yoon^1,2,3,4²  Dong-Hou Kim^1,2,3,4⁴ 

[1] Alzheimer’s Disease Experts Lab (ADEL), Asan Medical Center^1;Bio-Medical Institute of Technology (BMIT)^3;Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea^4;Department of Brain Science^2

关键词: Alzheimer disease (AD);   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer’s disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.

【 授权许可】

Unknown