Maruyama K, Usami M, Kametani F, Tomita T, Iwatsubo T, Saido T C, Mori H, Ishiura S
Department of Molecular Biology, Tokyo Institute of Psychiatry, Kamikitazawa, Setagaya, Tokyo 156-8585, Japan.
Int J Mol Med. 2000 Mar;5(3):269-73. doi: 10.3892/ijmm.5.3.269.
Several mutations of presenilin (PS)-1, 2 result in early onset Alzheimer disease. Using the yeast two-hybrid system, the interaction between PS2 loop domain and the C-terminal region of mu-calpain was previously identified. Calpain is a calcium dependent-protease and there are two isoforms, m-calpain and mu-calpain, which differ in the calcium concentration required for activation. m-Calpain needs about 10(-3) M calcium ions, whereas mu-calpain about 10(-5) M. When PS and calpain were separately expressed in COS cells by cDNA transfection and then combined in vitro, or both were co-transfected to be co-expressed in vivo in COS cells, PS1 and PS2 reduced the casein proteolysis activity of m-calpain but not that of mu-calpain. Some of the PS mutations related to Alzheimer disease decreased this inhibitory activity. On the other hand, PS1 was cleaved by m-calpain and mu-calpain at a different site from those already reported (constitutive cleavage or alternative cleavage). These results suggest a regulatory function of presenilin on the calpain system.
早老素（PS）-1、2的几种突变会导致早发性阿尔茨海默病。利用酵母双杂交系统，先前已鉴定出PS2环结构域与微钙蛋白酶C末端区域之间的相互作用。钙蛋白酶是一种钙依赖性蛋白酶，有两种同工型，即m-钙蛋白酶和微钙蛋白酶，它们在激活所需的钙浓度上有所不同。m-钙蛋白酶需要约10^(-3) M的钙离子，而微钙蛋白酶需要约10^(-5) M。当通过cDNA转染在COS细胞中分别表达PS和钙蛋白酶，然后在体外进行组合，或者将两者共转染以在COS细胞中体内共表达时，PS1和PS2降低了m-钙蛋白酶的酪蛋白蛋白水解活性，但不降低微钙蛋白酶的活性。一些与阿尔茨海默病相关的PS突变降低了这种抑制活性。另一方面，PS1在与已报道的位点（组成性切割或选择性切割）不同的位点被m-钙蛋白酶和微钙蛋白酶切割。这些结果表明早老素对钙蛋白酶系统具有调节功能。
