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...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.展开更多
粘附分子通过介导细胞间相互作用发挥其在发育、再生和突触修饰等方面的重要作用.神经细胞粘附分子CHL1(close homologue of L1)是近年发现的粘附分子,属于粘附分子免疫球蛋白超家族,集中表达于神经系统,通过亲异性作用(heterophilic in...粘附分子通过介导细胞间相互作用发挥其在发育、再生和突触修饰等方面的重要作用.神经细胞粘附分子CHL1(close homologue of L1)是近年发现的粘附分子,属于粘附分子免疫球蛋白超家族,集中表达于神经系统,通过亲异性作用(heterophilic interaction)介导细胞与细胞、细胞与胞外基质的相互作用,进而参与神经系统的发育、轴突的生长、迁移及导向等过程.展开更多
文摘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.
文摘粘附分子通过介导细胞间相互作用发挥其在发育、再生和突触修饰等方面的重要作用.神经细胞粘附分子CHL1(close homologue of L1)是近年发现的粘附分子,属于粘附分子免疫球蛋白超家族,集中表达于神经系统,通过亲异性作用(heterophilic interaction)介导细胞与细胞、细胞与胞外基质的相互作用,进而参与神经系统的发育、轴突的生长、迁移及导向等过程.
