Differential localization of protein phosphatase-1α, β and γ1 isoforms in primate prefrontal cortex
Differential localization of protein phosphatase-1α, β and γ1 isoforms in primate prefrontal cortex
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DOI：
10.1093/cercor/bhi070
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发表时间：
2005-12-01
期刊：
影响因子：
3.7
通讯作者：
Muly, EC
中科院分区：
文献类型：
--
作者：
Bordelon, JR;Smith, Y;Muly, EC
前额叶皮质功能依赖于D1家族受体及其复杂的信号转导级联，包括蛋白磷酸酶-1（PP 1）。三种PP 1亚型在大脑中是突出的：PP 1 α，PP 1 β和PP 1 γ 1。PP 1定位的各种支架蛋白是至关重要的多巴胺介导的调制的多巴胺能神经传递。我们已经定量的亚细胞分布的灵长类动物前额叶皮层，使用免疫电镜。所有这三种都存在于棘、树突、轴突终末、轴突和神经胶质中。然而，PP 1 α和PP 1 γ 1标记在棘中富集，而PP 1 β标记在树突中富集。使用包埋后免疫金标记，我们进一步研究了PP 1 α和PP 1 γ 1在棘内的分布。PP 1 γ 1高度特异性地集中在这些棘的突触后密度（PSD）中，而PP 1 α在PSD中富集，但也以中等量在PSD下发现。因此，PP 1亚型不均匀地分布在皮质神经元和脊柱内。这些结果表明，每个PP 1亚型有机会获得一组不同的基板，此外，他们表明，信号转导蛋白的组成不同的神经元的不同部位，甚至在灵长类PFC的树突棘的不同区域。
Prefrontal cortical functioning depends on D1 family receptors and their complex signal transduction cascade, including protein phosphatase-1 (PP1). Three PP1 isoforms are prominent in the brain: PP1 alpha, PP1 beta and PP1 gamma 1. PP1 localization by a variety of scaffolding proteins is critical for dopamine-mediated modulation of glutamatergic neurotransmission. We have quantified the subcellular distribution of each isoform in primate prefrontal cortex using immunoelectron microscopy. All three are found in spines, dendrites, axon terminals, axons and glia. However, PP1 alpha and PP1 gamma 1 labeling is enriched in spines, whereas PP1 beta label is enriched in dendrites. Using post-embedding immunogold labeling, we further examined the distribution of PP1 alpha and PP1 gamma 1 within spines. PP1 gamma 1 is highly and specifically concentrated in the postsynaptic density (PSD) of these spines, while PP1 alpha is enriched in the PSD but also found subjacent to the PSD in moderate amounts. Thus, PP1 isoforms are heterogeneously distributed in the cortical neuropil and within spines. These results suggest that each PP1 isoform has access to a different set of substrates and, furthermore, they demonstrate that the composition of signal transduction proteins varies in different parts of the neuron and even in different regions of a dendritic spine in the primate PFC.