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KMID : 0624620160490060337
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BMB Reports
2016 Volume.49 No. 6 p.337 ~ p.342
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Regulation of amyloid precursor protein processing by its KFERQ motif
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Park Ji-Seon
Kim Dong-Hou
Yoon Seung-Yong
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Abstract
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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.
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KEYWORD
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Alzheimer disease (AD), β-amyloid, Chaperone mediated autophagy, Hsc70, LAMP2
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