Blazejczyk Magdalena, Wojda Urszula, Sobczak Adam, Spilker Christina, Bernstein Hans-Gert, Gundelfinger Eckart D, Kreutz Michael R, Kuznicki Jacek
Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland.
Biochim Biophys Acta. 2006 Jan;1762(1):66-72. doi: 10.1016/j.bbadis.2005.09.006. Epub 2005 Oct 14.
The interaction between the EF-hand Ca(2+)-binding protein calmyrin and presenilin 2 (PS2) has been suggested to play a role in Alzheimer's disease (AD). We now report that calmyrin binds specifically endogenous PS2 and not PS1. However, binding appears to be Ca(2+)-independent and calmyrin does not exhibit a Ca(2+)-dependent translocation to intracellular membranes as demonstrated in a Ca(2+)-myristoyl switch assay. Moreover, calmyrin is only present at very low levels in brain areas associated with the onset of AD. In rat, forebrain calmyrin is localized only in a subset of principal neurons, similarly as in human forebrain. Finally, subcellular fractionation demonstrates only a limited overlap of calmyrin and PS2 at neuronal membranes. We therefore conclude that calmyrin will not contribute significantly as a Ca(2+)-sensor that transduces Ca(2+)-signaling events to PS2 in forebrain.
EF 手型钙结合蛋白钙调素（calmyrin）与早老素 2（PS2）之间的相互作用被认为在阿尔茨海默病（AD）中发挥作用。我们现在报告，钙调素特异性结合内源性 PS2 而非 PS1。然而，这种结合似乎不依赖于钙离子，并且在钙离子 - 肉豆蔻酰开关分析中表明，钙调素不会表现出依赖钙离子的向细胞内膜的转位。此外，钙调素在与 AD 发病相关的脑区中仅以极低水平存在。在大鼠中，前脑钙调素仅定位于一部分主要神经元中，与人类前脑情况类似。最后，亚细胞分级分离表明钙调素和 PS2 在神经元膜上仅有有限的重叠。因此，我们得出结论，钙调素作为一种将钙离子信号事件转导至前脑 PS2 的钙离子传感器，不会有显著作用。
