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首页> 外文期刊>The European Journal of Neuroscience >Nuclear localization of diacylglycerol kinase zeta in neurons.
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Nuclear localization of diacylglycerol kinase zeta in neurons.

机译：二酰基甘油激酶zeta在神经元中的核定位。

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摘要

Diacylglycerol kinase (DGK) is involved in intracellular signal transduction as a regulator of levels of diacylglycerol which leads to protein kinase C activation. Previous studies have revealed that DGK consists of a family of isozymes in mammalian species and that most if not all of them show abundant expression in the central nervous system, suggesting the importance of this enzyme in neuronal function. Among the isozymes, DGK zeta (previously also known as DGK-IV for the rat clone) has unique structural features, such as four ankyrin-like repeats and a nuclear localization signal (NLS), and shows intense mRNA expression in neurons of the olfactory bulb, hippocampus and cerebral and cerebellar cortices (Goto, K. & Kondo, H. (1996), Proc. Natl Acad. Sci. USA, 93, 11196-11201). However, previous studies have given conflicting results about whether or not DGK zeta localizes to the nucleus in these cells. In this study, we have used immunohistochemistry with specific antibodies in brain tissues and cDNAtransfection into primary cultured neurons to address this question. We have shown that, while DGK zeta is primarily a nuclear protein in neurons, it can also be cytoplasmic in some conditions, and the subcellular location depends not only on the cell type but also on the developmental state or growth conditions of the cell. In addition, we have used deletion mutants to show that nuclear transport of DGK zeta depends on a cooperative interaction between the NLS and the C-terminal region including ankyrin repeats in a manner which suggests that the NLS is a cryptic site whose exposure is regulated by the C-terminal region. Together, these results support the hypothesis that the localization of DGK zeta may be regulated by differential expression of these various proteins which interact with its C-terminal region.
机译：二酰基甘油激酶（DGK）作为导致蛋白质激酶C活化的二酰基甘油水平的调节剂，参与细胞内信号转导。先前的研究表明，DGK由哺乳动物物种中的一个同功酶家族组成，大多数（如果不是全部的话）它们在中枢神经系统中显示出丰富的表达，表明该酶在神经元功能中的重要性。在同工酶中，DGK zeta（以前也称为大鼠克隆的DGK-IV）具有独特的结构特征，例如四个锚蛋白样重复序列和核定位信号（NLS），并在嗅觉神经元中显示出强烈的mRNA表达。鳞茎，海马以及大脑和小脑皮质（Goto，K.＆Kondo，H.（1996），美国国家科学院学报，93，11196-11201）。但是，先前的研究对于DGK zeta是否位于这些细胞的核中给出了矛盾的结果。在这项研究中，我们将免疫组织化学与脑组织中的特定抗体一起使用，并将cDNA转染到原代培养的神经元中，以解决这个问题。我们已经表明，虽然DGK zeta主要是神经元中的核蛋白，但在某些情况下它也可以是细胞质的，并且亚细胞的位置不仅取决于细胞类型，还取决于细胞的发育状态或生长条件。此外，我们已经使用缺失突变体来显示DGK zeta的核转运取决于NLS与包括锚蛋白重复序列​​的C端区域之间的协同相互作用，这表明NLS是一个受暴露调节的隐蔽位点。 C末端区域。总之，这些结果支持了以下假设：DGK zeta的定位可能受这些与C末端区域相互作用的各种蛋白质的差异表达所调节。

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