Na,K-ATPase and the role of α isoforms in behavior
Na,K-ATPase and the role of α isoforms in behavior
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DOI：
10.1007/s10863-007-9107-9
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发表时间：
2007-12-01
影响因子：
3
通讯作者：
Moseley, Amy E.
中科院分区：
文献类型：
--
作者：
Lingrel, Jerry B.;Williams, Michael T.;Moseley, Amy E.
Na，K-ATPase由多种亚型组成，亚型分布随组织发育不同而不同。例如，在肾脏和许多其他组织中，α1亚型是主要的亚型，而在骨骼肌中，α2亚型是主要的亚型。这三种亚型均存在于脑中，但在成年啮齿动物脑中，α3亚型主要位于神经元中，而α2亚型主要存在于星形胶质细胞和一些有限的神经元群体中。有趣的是，阿尔法4亚型仅存在于精子尾部的中间区域。Na，K-ATPase亚型在许多组织和发育过程中的分布已经得到了广泛的研究。以上列举的例子为Na，K-ATPase亚型表达的多样性提供了一些迹象。为了了解这种分布的意义，我们培育了缺乏α1、α2和α3亚型的动物。预计这些研究将深入了解这些异构体在驱动特定组织中的各种生物学过程中所起的作用。在这里，我们描述了我们的一些研究，这些研究涉及阿尔法1、阿尔法2和阿尔法3缺陷小鼠的行为方面，特别是那些在一个亚型中单倍体不足的小鼠，即缺乏阿尔法1、阿尔法2或阿尔法3亚型的一个功能基因。这类研究很重要，因为有两种人类疾病与阿尔法2和阿尔法3亚型缺陷有关。这两种疾病分别是家族性偏瘫2型偏头痛和速发型发育迟缓性帕金森综合征，分别由α2和α3亚型单倍体功能不全引起。我们发现，α2和α3亚型的单倍体不足会导致行为缺陷。
The Na,K-ATPase is composed of multiple isoforms and the isoform distribution varies with the tissue and during development. The alpha 1 isoform for example, is the major isoform in the kidney and many other tissues, while the alpha 2 isoform is the predominate one in skeletal muscle. All three isoforms are found in the brain although in adult rodent brain, the alpha 3 isoform is located essentially in neurons while the alpha 2 isoform is found in astrocytes and some limited neuronal populations. Interestingly the alpha 4 isoform is found exclusively in the mid region of the sperm tail. The distribution of the isoforms of the Na,K-ATPase has been extensively studied in many tissues and during development. The examples cited above provide some indication to the diversity of Na,K-ATPase isoform expression. In order to understand the significance of this distribution, we have developed animals which lack the alpha 1, alpha 2, and alpha 3 isoforms. It is anticipated that these studies will provide insight into the role that these isoforms play in driving various biological processes in specific tissues. Here we describe some of our studies which deal with the behavioral aspects of the alpha 1, alpha 2, and alpha 3 deficient mice, particularly those that are haploinsufficient in one isoform i.e. lacking one functional gene for the alpha 1, alpha 2, or alpha 3 isoforms. Such studies are important as two human diseases are associated with deficiency in the alpha 2 and alpha 3 isoforms. These are Familial Hemiplegic Migraine type 2 and Rapid-Onset Dystonia Parkinsonism, these diseases result from alpha 2 and alpha 3 isoform haploinsufficiency, respectively. We find that the haploinsufficiency of both alpha 2 and alpha 3 isoforms result in behavioral defects.