Subcellular distribution of neurabin immunolabeling in primate prefrontal cortex: Comparison with spinophilin
Subcellular distribution of neurabin immunolabeling in primate prefrontal cortex: Comparison with spinophilin
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DOI：
10.1093/cercor/bhh101
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发表时间：
2004-12-01
期刊：
影响因子：
3.7
通讯作者：
Greengard, P
中科院分区：
文献类型：
--
作者：
Muly, EC;Allen, P;Greengard, P
前额叶皮质的功能依赖于多巴胺能神经传递，而多巴胺能神经传递又依赖于包括蛋白磷酸酶-1(PP1)在内的复杂信号转导途径。在多巴胺能调节谷氨酸神经递质的过程中，PP1的靶向定位是由骨架蛋白SPIN和Neurabin实现的。在这项研究中，我们报道了神经肽的抗血清的制备，并用它来研究神经肽的亚细胞定位，并与我们之前对亲刺蛋白的研究进行了比较，刺亲蛋白是一种密切相关的PP1支架。Neurabin主要存在于树突棘中，但也存在于其他隔室，包括树突、轴突、终末和神经胶质细胞。这种分布与亲刺素的分布不同，因为神经肽存在于没有亲刺素的轴突终末，而在含有小白蛋白的神经元间树突中，虽然树突中含有大量的亲刺素，但并不存在明显的神经肽。然而，在树突棘室内，这两种蛋白质的分布相似。Neurabin和Spin都集中在脊椎中，双重标记显示它们在大多数脊椎中共定位。此外，包埋后的免疫金标记法表明，在脊髓内，Neurabin的分布模式与Spin相同，集中在突触后密度和正下方的100 nm处。这些结果表明神经肽和刺激素在它们的分布模式上有重要的相似和不同之处。不同的支架定位模式可能在决定不同神经元群体或隔室中信号转导通路的内容和作用方面发挥重要作用。
Prefrontal cortical functioning depends on dopaminergic neurotransmission, which in turn depends on a complex signal transduction pathway including protein phosphatase-1 PP1). Targeted localization of PP1 by the scaffolding proteins, spinophilin and neurabin, is critical for dopaminergic modulation of glutamate neurotransmission. In this study, we report the preparation of an antiserum to neurabin, use it to study the subcellular localization of neurabin and compare that to our previous study of spinophilin, a closely related PP1 scaffold. Neurabin is found predominately in dendritic spines, but is also found in other compartments, including dendrites, axons, terminals and glia. This distribution contrasts with that of spinophilin in that neurabin is found in axon terminals where spinophilin is absent, and in parvalbumin-containing interneuron dendrites there is no significant neurabin though these dendrites contain substantial spinophilin. Within the dendritic spine compartment, however, the two proteins are similarly distributed. Both neurabin and spinophilin are concentrated in spines, and double-labeling reveals that they co-localize in most spines. Furthermore, post-embedding immunogold labeling demonstrates that within a spine, neurabin is distributed in the same pattern as spinophilin, concentrated in the postsynaptic density and the 100 nm just below. These results indicate that neurabin and spinophilin share important similarities and differences in their patterns of distribution. Varying patterns of scaffold localization may play an important role in determining the content and action of signal transduction pathways in different neuronal populations or compartments.