Li Xiaofan, Bürklen Tanja, Yuan Xianglin, Schlattner Uwe, Desiderio Dominic M, Wallimann Theo, Homayouni Ramin
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Mol Cell Neurosci. 2006 Feb;31(2):263-72. doi: 10.1016/j.mcn.2005.09.015. Epub 2005 Nov 2.
Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease (AD). However, the physiological role of APP and its family members is still unclear. To gain insights into APP function, we used a proteomic approach to identify APP interacting proteins. We report here for the first time a direct interaction between the C-terminal region of APP family proteins and ubiquitous mitochondrial creatine kinase (uMtCK). This interaction was confirmed in vitro as well as in cultured cells and in brain. Interestingly, expression of full-length and C-terminal domain of APP family proteins stabilized uMtCK preprotein in cultured cells. Our data suggest that APP may regulate cellular energy levels and mitochondrial function via a direct interaction and stabilization of uMtCK.
淀粉样前体蛋白（APP）参与阿尔茨海默病（AD）的发病机制。然而，APP及其家族成员的生理作用仍不清楚。为深入了解APP的功能，我们采用蛋白质组学方法来鉴定与APP相互作用的蛋白质。我们首次在此报告APP家族蛋白的C末端区域与普遍存在的线粒体肌酸激酶（uMtCK）之间存在直接相互作用。这种相互作用在体外、培养细胞和大脑中均得到证实。有趣的是，APP家族蛋白的全长和C末端结构域的表达在培养细胞中稳定了uMtCK前体蛋白。我们的数据表明，APP可能通过与uMtCK的直接相互作用和稳定作用来调节细胞能量水平和线粒体功能。
