A-kinase anchoring protein 150 expression in a specific subset of TRPV1- and CaV 1.2-positive nociceptive rat dorsal root ganglion neurons.
A-kinase anchoring protein 150 expression in a specific subset of TRPV1- and CaV 1.2-positive nociceptive rat dorsal root ganglion neurons.
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A-激酶锚定蛋白150在TRPV1和CAV 1.2阳性伤害性大鼠背根神经元的特定子集中表达。
DOI：
10.1002/cne.22692
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Levinson SR
中科院分区：
文献类型：
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作者：
Brandao KE;Dell'Acqua ML;Levinson SR
离子通道磷酸化状态的调节是炎症期间痛觉过敏发生的关键步骤。通道活性的调节增强可能会增加神经元的兴奋性并影响下游靶标，例如基因转录。这种离子通道调节所需的特异性通过支架 A 激酶锚定蛋白 79/150 (AKAP79/150) 靶向蛋白激酶和磷酸酶而快速实现。 AKAP79/150 通过将 PKA 和 PKC 靶向外周感觉神经元中的 TRPV1 通道，从而降低多种炎症试剂的激活阈值，从而与炎症疼痛有关。然而，AKAP79/150 在外周感觉神经元中的表达模式尚不清楚。在本研究中，我们使用免疫荧光显微镜来识别 DRG 切片中表达啮齿动物亚型 AKAP150 的周围神经元亚型，以及 AKAP150 的亚细胞分布及其潜在的靶离子通道。我们发现 AKAP150 主要在小 DRG 感觉神经元的子集中表达，其位于胞体、轴突初始段和小纤维的质膜上。这些神经元中的大多数是外周蛋白阳性并产生 c 纤维，尽管一小部分产生 Aδ 纤维。此外，我们证明 AKAP79/150 与 TRPV1 和 CaV1.2 在体细胞和轴突初始段共定位。因此，AKAP150 在小的伤害性 DRG 神经元中表达，它靶向膜区域，并且可能在调节痛觉过敏所需的离子通道磷酸化状态中发挥作用。
Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and phosphatases by the scaffolding A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 has been implicated in inflammatory pain by targeting PKA and PKC to the TRPV1 channel in peripheral sensory neurons, thus lowering threshold for activation by multiple inflammatory reagents. However, the expression pattern of AKAP79/150 in peripheral sensory neurons is unknown. In this study we use immunofluorescence microscopy to identify in DRG sections the peripheral neuron subtypes that express the rodent isoform AKAP150, as well as the subcellular distribution of AKAP150 and its potential target ion channels. We found that AKAP150 is predominantly expressed in a subset of small DRG sensory neurons where it is localized at the plasma membrane of the soma, axon initial segment and small fibers. The majority of these neurons is peripherin positive and produces c-fibers, though a small portion produces Aδ-fibers. Furthermore, we demonstrate that AKAP79/150 colocalizes with TRPV1 and CaV1.2 in the soma and axon initial segment. Thus AKAP150 is expressed in small, nociceptive DRG neurons where it is targeted to membrane regions and where it may play a role in the modulation of ion channel phosphorylation states required for hyperalgesia.