A novel family of transmembrane proteins interacting with β subunits of the Na,K-ATPase
A novel family of transmembrane proteins interacting with β subunits of the Na,K-ATPase
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DOI：
10.1093/hmg/ddm167
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发表时间：
2007-10-15
影响因子：
3.5
通讯作者：
Heintz, Nathaniel
中科院分区：
文献类型：
--
作者：
Gorokhova, Svetlana;Bibert, Stephanie;Heintz, Nathaniel
我们的特点是一个家庭组成的四个哺乳动物蛋白的未知功能（NKAIN 1，2，3和4）和一个单一的果蝇直系同源dNKAIN。除了高度保守的跨膜结构域，NKAIN蛋白不含特征性功能结构域。前两个跨膜结构域中引人注目的氨基酸保守性表明这些蛋白质可能在膜双层内起作用。NKAIN家族成员在小鼠脑的多个区域中神经元表达，尽管它们的表达不是普遍存在的。我们证明，小鼠NKAIN 1与Na，K-ATP酶的β 1亚基相互作用，而果蝇直系同源物dNKAIN与Nrv2.2相互作用，Nrv2.2是Na，K-ATP酶β亚基的果蝇同源物。我们还表明，NKAIN 1可以形成一个复合物与另一个β亚基结合蛋白，MONaKA，当结合到钠，钾-ATP酶的β 1亚基。我们的研究结果表明，哺乳动物NKAIN 1和MONaKA之间的复合物是NKAIN功能所必需的，这是由一个单一的蛋白质，dNKAIN，在果蝇。这一假设得到以下事实的支持：dNKAIN而不是NKAIN 1诱导电压非依赖性阿米洛利不敏感的Na+比电导，其可以被镧阻断。由于在dNKAIN基因中插入P元件而导致dNKAIN表达降低的果蝇突变体表现出温度敏感性麻痹，这也是由Na，K-ATP酶α亚基和几种离子通道的突变引起的表型。NKAIN蛋白质的神经元表达，其膜定位和NKAIN果蝇突变体的温度敏感性麻痹强烈表明，这种新的蛋白质家族可能是神经元功能的关键。
We characterized a family consisting of four mammalian proteins of unknown function (NKAIN1, 2, 3 and 4) and a single Drosophila ortholog dNKAIN. Aside from highly conserved transmembrane domains, NKAIN proteins contain no characterized functional domains. Striking amino acid conservation in the first two transmembrane domains suggests that these proteins are likely to function within the membrane bilayer. NKAIN family members are neuronally expressed in multiple regions of the mouse brain, although their expression is not ubiquitous. We demonstrate that mouse NKAIN1 interacts with the beta 1 subunit of the Na, K-ATPase, whereas Drosophila ortholog dNKAIN interacts with Nrv2.2, a Drosophila homolog of the Na, K-ATPase beta subunits. We also show that NKAIN1 can form a complex with another beta subunit-binding protein, MONaKA, when binding to the beta 1 subunit of the Na,K-ATPase. Our results suggest that a complex between mammalian NKAIN1 and MONaKA is required for NKAIN function, which is carried out by a single protein, dNKAIN, in Drosophila. This hypothesis is supported by the fact that dNKAIN, but not NKAIN1, induces voltage-independent amiloride-insensitive Na+-specific conductance that can be blocked by lanthanum. Drosophila mutants with decreased dNKAIN expression due to a P-element insertion in the dNKAIN gene exhibit temperature-sensitive paralysis, a phenotype also caused by mutations in the Na, K-ATPase alpha subunit and several ion channels. The neuronal expression of NKAIN proteins, their membrane localization and the temperature-sensitive paralysis of NKAIN Drosophila mutants strongly suggest that this novel protein family may be critical for neuronal function.