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锚蛋白B调节钠钾ATP酶/肌醇1,4,5-三磷酸受体信号微结构域的功能。

Ankyrin B modulates the function of Na,K-ATPase/inositol 1,4,5-trisphosphate receptor signaling microdomain.

作者信息

Liu Xiao, Spicarová Zuzana, Rydholm Susanna, Li Juan, Brismar Hjalmar, Aperia Anita

机构信息

Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Q2:09, SE-171 76 Stockholm, Sweden.

出版信息

J Biol Chem. 2008 Apr 25;283(17):11461-8. doi: 10.1074/jbc.M706942200. Epub 2008 Feb 26.

Abstract

Na,K-ATPase and inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) can form a signaling microdomain that in the presence of ouabain triggers highly regular calcium oscillations. Downstream effects include NF-kappaB activation. Here we report that ankyrin B (Ank-B), expressed in most mammalian cells, plays a pivotal role in the function of the Na,K-ATPase/IP3R signaling microdomain. In studies performed on a monkey kidney cell line, we show that Ank-B co-precipitates with both Na,K-ATPase and IP3R. We identify the N terminus tail of the Na,K-ATPase catalytic subunit and the N-terminal portion 1-604 of the IP3R as novel binding sites for Ank-B. Knockdown of Ank-B with small interfering RNA reduced the expression of Ank-B to 15-30%. This down-regulation of Ank-B attenuated the interaction between Na,K-ATPase and IP3R, reduced the number of cells responding to pm doses of ouabain with calcium oscillations, altered the calcium oscillatory pattern, and abolished the ouabain effect on NF-kappaB. In contrast, Ank-B down-regulation had no effect on the ion transporting function of Na,K-ATPase and no effect on the distribution and apparent mobility of Na,K-ATPase in the plasma membrane.

摘要

钠钾ATP酶与肌醇1,4,5 - 三磷酸(IP3)受体(IP3R)可形成一个信号微结构域,在哇巴因存在的情况下触发高度规则的钙振荡。下游效应包括核因子κB(NF-κB)的激活。在此我们报告,在大多数哺乳动物细胞中表达的锚蛋白B(Ank-B)在钠钾ATP酶/IP3R信号微结构域的功能中起关键作用。在对一种猴肾细胞系进行的研究中,我们发现Ank-B与钠钾ATP酶和IP3R都能共沉淀。我们确定钠钾ATP酶催化亚基的N末端尾巴以及IP3R的N末端1 - 604部分是Ank-B的新结合位点。用小干扰RNA敲低Ank-B可使Ank-B的表达降至15% - 30%。Ank-B的这种下调减弱了钠钾ATP酶与IP3R之间的相互作用,减少了对皮摩尔剂量哇巴因产生钙振荡反应的细胞数量,改变了钙振荡模式,并消除了哇巴因对NF-κB的作用。相比之下,Ank-B的下调对钠钾ATP酶的离子转运功能没有影响,对钠钾ATP酶在质膜中的分布和表观迁移率也没有影响。

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