Region- and neuronal-subtype-specific expression of Na,K-ATPase alpha and beta subunit isoforms in the mouse brain.
Region- and neuronal-subtype-specific expression of Na,K-ATPase alpha and beta subunit isoforms in the mouse brain.
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DOI：
10.1002/cne.24924
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发表时间：
2020-11-01
期刊：
影响因子：
--
通讯作者：
Fukazawa Y
中科院分区：
文献类型：
--
作者：
Murata K;Kinoshita T;Ishikawa T;Kuroda K;Hoshi M;Fukazawa Y
Na，K-ATPase是一种普遍存在的分子，与Na+和K+离子在质膜上的不对称分布和维持膜电位有关，而膜电位是神经元活动的先决条件。Na，K-ATPase由α，β和FXYD三个亚基组成。在小鼠中，α亚基有四种亚型，其中三种(α1、α2和α3)在大脑中表达。然而，不同大脑亚型的功能和生物学意义仍有待充分阐明。最近的研究表明，编码α3亚单位的基因ATP1A3与神经疾病有关。为了定位α亚基异构体的细胞分布及其共表达模式，我们用原位杂交的方法研究了ATP1A1、ATP1A2和ATP1A3mRNA在小鼠脑中的表达。Atp1a1和ATP1a3在神经元中表达，而Atp1a2几乎仅在神经胶质细胞中表达。大多数神经元共表达Atp1a1和ATP1A3，在不同脑区和神经元亚型中的表达水平高度不同。我们发现在海马、体感皮质和脾后皮质表达小白蛋白(PV)的GABA能神经元是低ATP1a1和高ATP1A3的神经元亚型的一个例子。Atp1b亚型的表达在不同脑区和不同细胞亚型之间也是不同的。PV阳性神经元高水平表达Atp1b1，低水平表达Atp1b2和Atp1b3。这些发现提供了区域和神经元亚型依赖的Na，K-ATPaseα和β亚单位亚型表达的基本信息，并为高表达ATP1A3的神经元选择性参与神经疾病提供了理论基础。Na，K-ATPase包括α(Atp1a)、β(Atp1b)和FXYD亚基，每个亚基都有亚型。α和β亚基异构体的原位杂交显示，异构体在小鼠脑中的表达具有区域和神经元亚型特异性。图为ATP1a1(红色)和ATP1A3(绿色)在海马齿状回的表达(DAPI染色，蓝色)。
Na,K‐ATPase is a ubiquitous molecule contributing to the asymmetrical distribution of Na+ and K+ ions across the plasma membrane and maintenance of the membrane potential, a prerequisite of neuronal activity. Na,K‐ATPase comprises three subunits (α, β, and FXYD). The α subunit has four isoforms in mice, with three of them (α1, α2, and α3) expressed in the brain. However, the functional and biological significances of the different brain isoforms remain to be fully elucidated. Recent studies have revealed the association of Atp1a3, a gene encoding α3 subunit, with neurological disorders. To map the cellular distributions of the α subunit isoforms and their coexpression patterns, we evaluated the mRNA expression of Atp1a1, Atp1a2, and Atp1a3 by in situ hybridization in the mouse brain. Atp1a1 and Atp1a3 were expressed in neurons, whereas Atp1a2 was almost exclusively expressed in glial cells. Most neurons coexpressed Atp1a1 and Atp1a3, with highly heterogeneous expression levels across the brain regions and neuronal subtypes. We identified parvalbumin (PV)‐expressing GABAergic neurons in the hippocampus, somatosensory cortex, and retrosplenial cortex as an example of a neuronal subtype expressing low Atp1a1 and high Atp1a3. The expression of Atp1b isoforms was also heterogeneous across brain regions and cellular subtypes. The PV‐expressing neurons expressed a high level of Atp1b1 and a low level of Atp1b2 and Atp1b3. These findings provide basic information on the region‐ and neuronal‐subtype‐dependent expression of Na,K‐ATPase α and β subunit isoforms, as well as a rationale for the selective involvement of neurons expressing high levels of Atp1a3 in neurological disorders. Na,K‐ATPase comprises α (Atp1a), β (Atp1b), and FXYD subunits, and each subunit has isoforms. In situ hybridization for α and β subunit isoforms revealed regional‐ and neuronal‐subtype‐specific expression of the isoforms in the mouse brain. The photograph shows Atp1a1 (red) and Atp1a3 (green) expression in the hippocampal dentate gyrus (stained with DAPI, blue).
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