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Regulation of amyloid precursor protein processing by its KFERQ motif
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  • Journal title : BMB Reports
  • Volume 49, Issue 6,  2016, pp.337-343
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.6.212
 Title & Authors
Regulation of amyloid precursor protein processing by its KFERQ motif
Park, Ji-Seon; Kim, Dong-Hou; Yoon, Seung-Yong;
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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.
Alzheimer disease (AD);β-amyloid;Chaperone mediated autophagy;Hsc70;LAMP2;
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