α-secretase ADAM IO physically interacts with β-secretase BACE1 in neurons and regulates CHL1 proteolysis  

作　　者：Xin Wang Congcong Wang Gang Pei 

机构地区：[1]State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China [2]Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China

出　　处：《Journal of Molecular Cell Biology》2018年第5期411-422,共12页分子细胞生物学报（英文版）

摘　　要：α-secretase and β-secretase are known to compete for amyloid precursor protein （APP） processing and thus play a vital role in Alzheimer＇s disease pathogenesis. A disintegrin and metaUoproteinase 10 （ADAM10） and β-site APP cleaving enzyme 1 （BACE1） mediate the major activities of α-secretase and β-secretase in brain and share various common substrates. However, whether they function separately or together is poorly understood. Here, we show that ADAM10 and BACE1 co-localize in the neurites of mouse primary neurons. Co-immunoprecipitation and fluorescence resonance energy transfer analysis revealed that ADAM10 and BACE1 interact with each other under both endogenous and exogenous conditions. In addition, we found that ADAMIO enhances the proteolysis of neural cell adhesion molecule close homolog of L1 （CHL1） by BACE1. Further studies found that ADAM10-BACE1 interaction interfering peptide LT52 attenuates the regulation of ADAM10 on BACEl-mediated cleavage of CHL1. Our data indicate that ADAM10-BACE1 interaction regulates the proteolysis of some specific substrates and may play a potential role in brain function.

关 键 词：SECRETASE Alzheimer＇s disease ADAM10 BACE1 interact APP CHL1 

分 类 号：Q421[生物学—神经生物学] TG659[生物学—生理学]