Department of Biomedicine, Institute of Physiology, University of Basel, Basel, Switzerland.
J Comp Neurol. 2011 Jun 1;519(8):1435-54. doi: 10.1002/cne.22610.
GABA(B) receptors are the G-protein-coupled receptors for γ-aminobutyric acid (GABA). KCTD8, 12, 12b, and 16 were recently identified as auxiliary GABA(B) receptor subunits and distinctly influence biophysical and pharmacological properties of the receptor response. Here we examined the expression patterns of the KCTDs in the mouse brain. Using in situ hybridization analysis, we found that most neurons express KCTD transcripts, supporting biochemical data showing that most GABA(B) receptors in the brain incorporate KCTD proteins. In the adult brain, KCTD12 and 16 have a widespread and KCTD8 and 12b a restricted expression pattern. Individual neurons can coexpress multiple KCTDs, as shown for granule cells and CA1/CA3 pyramidal cells in the hippocampus that coexpress KCTD12 and 16. In contrast, granule, Purkinje, and Golgi cells in the cerebellum selectively express one KCTD at a time. The expression levels of individual KCTD transcripts vary during postnatal brain development. Immunohistochemistry reveals that individual KCTD proteins can exhibit distinct axonal or dendritic localizations in neuronal populations. KCTDs are also detectable in nonneuronal tissues not expected to express GABA(B) receptors, suggesting that the role of KCTD proteins extends beyond GABA(B) receptors. In summary, our findings support that most brain GABA(B) receptors associate with KCTD proteins, but that the repertoire and abundance of KCTDs varies during development, among brain areas, neuronal populations, and at subcellular sites. We propose that the distinct spatial and temporal KCTD distribution patterns underlie functional differences in native GABA(B) responses.
GABA(B) 受体是 γ-氨基丁酸 (GABA) 的 G 蛋白偶联受体。最近发现 KCTD8、12、12b 和 16 是 GABA(B) 受体的辅助亚基，并显著影响受体反应的生物物理和药理学特性。在这里，我们研究了 KCTD 在小鼠大脑中的表达模式。通过原位杂交分析，我们发现大多数神经元表达 KCTD 转录本，支持生化数据表明大脑中的大多数 GABA(B) 受体都包含 KCTD 蛋白。在成年大脑中，KCTD12 和 16 具有广泛的表达模式，而 KCTD8 和 12b 的表达模式则受到限制。单个神经元可以共表达多种 KCTD，如海马体中的颗粒细胞和 CA1/CA3 锥体神经元共表达 KCTD12 和 16。相比之下，小脑的颗粒、浦肯野和高尔基细胞一次只选择性表达一种 KCTD。个体 KCTD 转录本的表达水平在出生后大脑发育过程中发生变化。免疫组织化学显示，个体 KCTD 蛋白在神经元群体中可以表现出不同的轴突或树突定位。在不预期表达 GABA(B) 受体的非神经元组织中也可以检测到 KCTD，这表明 KCTD 蛋白的作用超出了 GABA(B) 受体。总之，我们的研究结果支持大多数大脑 GABA(B) 受体与 KCTD 蛋白结合，但 KCTD 的种类和丰度在发育过程中、在不同脑区、神经元群体和亚细胞部位存在差异。我们提出，独特的空间和时间 KCTD 分布模式是内源性 GABA(B) 反应功能差异的基础。
