A-kinase anchoring protein 150 in the mouse brain is concentrated in areas involved in learning and memory

A-kinase anchoring protein 150 in the mouse brain is concentrated in areas involved in learning and memory
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DOI:
10.1016/j.brainres.2007.01.117
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发表时间:
2007-05
期刊:
影响因子:
2.9
通讯作者:
A. Ostroveanu;E. Zee;A. Dolga;P. Luiten;U. Eisel;I. Nijholt
A. Ostroveanu;E. Zee;A. Dolga;P. Luiten;U. Eisel;I. Nijholt
中科院分区:
医学3区
文献类型:
--
作者:
A. Ostroveanu;E. Zee;A. Dolga;P. Luiten;U. Eisel;I. Nijholt

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A-激酶锚定蛋白(AKAP)形成大分子信号传导复合物,其特异性地将cAMP依赖性蛋白激酶(PKA)靶向至独特的亚细胞区室,从而为PKA信号传导提供高特异性。例如,AKAP 79/150家族将PKA、PKC和PP 2B连接到神经元膜和突触后密度,并在突触功能中起重要作用。一些研究表明,AKAP 79/150锚定PKA有助于与突触可塑性和记忆过程相关的机制,但AKAP在这些过程中的确切作用仍然未知。在这项研究中,我们使用两种充分表征的AKAP 150抗体建立了AKAP 150的小鼠脑分布。使用Western blotting和免疫组织化学,我们发现AKAP 150广泛分布在整个小鼠脑中。AKAP 150在纹状体、大脑皮质和其他几个前脑区域(如嗅结节)中观察到最高表达水平,在海马和嗅球中发现相对高的表达,而在小脑、下丘脑、丘脑和脑干中发现低表达或无表达。尽管小鼠AKAP 150脑分布与大鼠脑分布相比存在一些微小差异,但我们的数据表明啮齿动物具有特征性AKAP 150脑分布模式。一般来说,我们观察到AKAP 150在参与学习和记忆的小鼠大脑区域中强烈表达。这些数据支持其在突触可塑性和记忆过程中的作用。
A-kinase anchoring proteins (AKAPs) form large macromolecular signaling complexes that specifically target cAMP-dependent protein kinase (PKA) to unique subcellular compartments and thus, provide high specificity to PKA signaling. For example, the AKAP79/150 family tethers PKA, PKC and PP2B to neuronal membranes and postsynaptic densities and plays an important role in synaptic function. Several studies suggested that AKAP79/150 anchored PKA contributes to mechanisms associated with synaptic plasticity and memory processes, but the precise role of AKAPs in these processes is still unknown. In this study we established the mouse brain distribution of AKAP150 using two well-characterized AKAP150 antibodies. Using Western blotting and immunohistochemistry we showed that AKAP150 is widely distributed throughout the mouse brain. The highest AKAP150 expression levels were observed in striatum, cerebral cortex and several other forebrain regions (e.g. olfactory tubercle), relatively high expression was found in hippocampus and olfactory bulb and low/no expression in cerebellum, hypothalamus, thalamus and brain stem. Although there were some minor differences in mouse AKAP150 brain distribution compared to the distribution in rat brain, our data suggested that rodents have a characteristic AKAP150 brain distribution pattern. In general we observed that AKAP150 is strongly expressed in mouse brain regions involved in learning and memory. These data support its suggested role in synaptic plasticity and memory processes.