title: Regulation of amyloid precursor protein processing by its KFERQ motif.
abstract: 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. [BMB Reports 2016; 49(6): 337-342].
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center; Department of Brain Science; Bio-Medical Institute of Technology (BMIT); Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Park
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center; Department of Brain Science; Bio-Medical Institute of Technology (BMIT); Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Dong-Hou
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center; Department of Brain Science; Bio-Medical Institute of Technology (BMIT); Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul 05505, Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D050883:HSC70 Heat-Shock Proteins; D016875:tau Proteins