Stabler S M, Ostrowski L L, Janicki S M, Monteiro M J
Medical Biotechnology Center and Department of Neurology, University of Maryland, Baltimore, Maryland 21201, USA.
J Cell Biol. 1999 Jun 14;145(6):1277-92. doi: 10.1083/jcb.145.6.1277.
It is well established that mutations in the presenilin 1 and 2 genes cause the majority of early onset Alzheimer's disease (AD). However, our understanding of the cellular functions of the proteins they encode remains rudimentary. Knowledge of proteins with which the presenilins interact should lead to a better understanding of presenilin function in normal and disease states. We report here the identification of a calcium-binding protein, calmyrin, that interacts preferentially with presenilin 2 (PS2). Calmyrin is myristoylated, membrane-associated, and colocalizes with PS2 when the two proteins are overexpressed in HeLa cells. Yeast two-hybrid liquid assays, affinity chromatography, and coimmunoprecipitation experiments confirm binding between PS2 and calmyrin. Functionally, calmyrin and PS2 increase cell death when cotransfected into HeLa cells. These results allude to several provocative possibilities for a dynamic role of calmyrin in signaling, cell death, and AD.
早有确凿证据表明，早老素1和2基因的突变会引发大多数早发型阿尔茨海默病（AD）。然而，我们对它们所编码蛋白质的细胞功能的了解仍然十分有限。了解与早老素相互作用的蛋白质，将有助于更好地理解早老素在正常和疾病状态下的功能。我们在此报告一种钙结合蛋白——钙调蛋白的鉴定结果，该蛋白优先与早老素2（PS2）相互作用。钙调蛋白经肉豆蔻酰化修饰，与膜相关，当这两种蛋白质在HeLa细胞中过表达时，它们会共定位。酵母双杂交液体分析、亲和色谱法和免疫共沉淀实验证实了PS2与钙调蛋白之间的结合。在功能上，钙调蛋白和PS2共转染到HeLa细胞中时会增加细胞死亡。这些结果暗示了钙调蛋白在信号传导、细胞死亡和AD中发挥动态作用的几种引人深思的可能性。
