The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses
The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses
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DOI：
10.1523/jneurosci.19-17-07300.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Fallon, JR
中科院分区：
文献类型：
--
作者：
Abbott, MA;Wells, DG;Fallon, JR
突触是神经系统中细胞间通讯的主要场所。现在清楚的是，除了经典的神经传递之外，突触还包含多种细胞信号传导方式。在这里，我们表明，两个组件的胰岛素通路定位在中枢神经系统突触，在那里他们的组件的突触后密度（PSD）。免疫化学筛选显示，58和53 kDa（p58/53）的多肽高度富集在大鼠大脑皮层，海马和小脑的PSD组分。这些多肽被纯化和微测序，揭示p58/53是相同的胰岛素受体酪氨酸激酶底物p58/53（IRSp53）。我们对IRSp58/53 mRNA的分析表明，在大鼠脑内有一个IRSp58和IRSp53的编码区，我们没有发现选择性剪接的证据。我们证明，IRSp58/53表达在小脑的突触丰富的分子层，并高度集中在培养的海马神经元的突触，在那里它与胰岛素受体共定位。总之，这些数据表明，胰岛素信号可能在中枢神经系统突触中发挥作用。
The synapse is the primary locus of cell-cell communication in the nervous system. It is now clear that the synapse incorporates diverse cell signaling modalities in addition to classical neurotransmission. Here we show that two components of the insulin pathway are localized at CNS synapses, where they are components of the postsynaptic density (PSD). An immunochemical screen revealed that polypeptides of 58 and 53 kDa (p58/53) were highly enriched in PSD fractions from rat cerebral cortex, hippocampus, and cerebellum. These polypeptides were purified and microsequenced, revealing that p58/53 is identical to the insulin receptor tyrosine kinase substrate p58/53 (IRSp53). Our analysis of IRSp58/53 mRNA suggests that within rat brain there is one coding region for IRSp58 and IRSp53; we find no evidence of alternative splicing. We demonstrate that IRSp58/53 is expressed in the synapse-rich molecular layer of the cerebellum and is highly concentrated at the synapses of cultured hippocampal neurons, where it colocalizes with the insulin receptor. Together, these data suggest that insulin signaling may play a role at CNS synapses.