Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Neurosci Lett. 2012 Apr 25;515(1):92-6. doi: 10.1016/j.neulet.2012.03.036. Epub 2012 Mar 21.
Homer is a scaffold protein in the postsynaptic density (PSD) and binds to the intracellular tail of group I metabotropic glutamate receptors (mGluRs). Although Homer contributes to the regulation of physiological function in synapses, the role of Homer proteins under pathophysiological conditions, such as cerebral ischemia, is still not fully clear. In the present study, we sought to determine whether transient focal cerebral ischemia would affect the level of Homer1 in the isolated-PSD fraction from rats. We showed that Homer1a (short form) and Homer1b/c (long form) as well as group I mGluR were localized in the cortical PSD. Cerebral ischemia decreased the content of Homer1a, which is a dominant-negative inhibitor of the long form of Homer proteins, in the PSD at 4 h of reperfusion without changing the level of Homer1a in cortical homogenates. On the other hand, the levels of Homer1b/c in the both PSD and homogenates were decreased at 24 h of reperfusion. These results suggest that these decreases in the level of Homer1 proteins after cerebral ischemia may contribute to the disturbance of synaptic function and subsequent development of cerebral ischemia.
Homer 是突触后密度（PSD）中的支架蛋白，与 I 型代谢型谷氨酸受体（mGluRs）的细胞内尾部结合。尽管 Homer 有助于调节突触中的生理功能，但 Homer 蛋白在病理生理条件下的作用，如脑缺血，仍不完全清楚。在本研究中，我们试图确定短暂性局灶性脑缺血是否会影响从大鼠中分离的 PSD 部分中 Homer1 的水平。我们表明 Homer1a（短形式）和 Homer1b/c（长形式）以及 I 型 mGluR 定位于皮质 PSD 中。脑缺血在再灌注 4 小时时降低了 PSD 中 Homer1a 的含量，而 Homer1a 在皮质匀浆中的水平没有改变。另一方面，再灌注 24 小时时，PSD 和匀浆中的 Homer1b/c 水平均降低。这些结果表明，脑缺血后 Homer1 蛋白水平的降低可能导致突触功能紊乱和随后的脑缺血发展。
