Mapping the regulator of G protein signaling 4 (RGS4): presynaptic and postsynaptic substrates for neuroregulation in prefrontal cortex.
Mapping the regulator of G protein signaling 4 (RGS4): presynaptic and postsynaptic substrates for neuroregulation in prefrontal cortex.
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DOI：
10.1093/cercor/bhn235
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发表时间：
2009-09
期刊：
影响因子：
3.7
通讯作者：
C. Paspalas;L. Selemon;A. Arnsten
中科院分区：
文献类型：
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作者：
C. Paspalas;L. Selemon;A. Arnsten
G 蛋白信号传导调节器 4 (RGS4) 通过 G 蛋白调节细胞内信号传导，并且在精神分裂症患者的前额皮质 (PFC) 中显着减少。因此，表征 RGS4 在单个神经元区室中的表达是了解其对单个 G 蛋白偶联受体 (GPCR) 作用的关键。在这里，我们提出了基于免疫金电子显微镜分析的猕猴 PFC 中 RGS4 蛋白的超微结构参考图。在体细胞中，所有标记都是非突触性的，并且与锥体神经元的地下池微区相关。细胞核显示出大部分免疫反应性。 RGS4 水平沿着近端顶端树突特别高，并且随着距胞体的距离显着降低；聚类标签出现在二阶分支的分叉处。在远端树突和棘中，发现该蛋白质位于对称和不对称突触的突触后密度的侧面或直接面对。轴突也表达 RGS4。事实上，突触前和突触后标记的密度和分布与轴突超微结构和已建立的突触类型相关。数据表明，RGS4 不仅可以调节突触后信号，还可以响应突触和非突触 GPCR 激活来调节突触前信号传导，对 PFC 细胞生理学的多个方面具有广泛但高度选择性的影响。
Regulator of G protein signaling 4 (RGS4) regulates intracellular signaling via G proteins and is markedly reduced in the prefrontal cortex (PFC) of patients with schizophrenia. Characterizing the expression of RGS4 within individual neuronal compartments is thus key to understanding its actions on individual G protein-coupled receptors (GPCRs). Here we present an ultrastructural reference map of RGS4 protein in macaque PFC based on immunogold electron microscopic analysis. At the soma, all labeling was asynaptic and affiliated with subsurface cistern microdomains of pyramidal neurons. The nucleus displayed most of immunoreactivity. RGS4 levels were particularly high along proximal apical dendrites and markedly decreased with distance from the soma; clustered label was present at the bifurcation into second-order branches. In distal dendrites and in spines, the protein was found flanking or directly facing the postsynaptic density of symmetric and asymmetric synapses. Axons also expressed RGS4. In fact, the density and distribution of pre- and postsynaptic labeling was correlated with the axon ultrastructure and the type of established synapses. The data indicate that RGS4 is strategically positioned to regulate not only postsynaptic but also presynaptic signaling in response to synaptic and nonsynaptic GPCR activation, having broad yet highly selective influences on multiple aspects of PFC cellular physiology.