The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties
The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties
复制标题
DOI：
10.1074/jbc.272.46.28819
复制
发表时间：
1997-11-14
影响因子：
4.8
通讯作者：
Lazdunski, M
中科院分区：
文献类型：
--
作者：
Bassilana, F;Champigny, G;Lazdunski, M
质子门控阳离子通道是存在于感觉神经元和中枢神经系统神经元中的酸传感器。其中一种酸感应离子通道（ASIC）最近被克隆。本研究表明，ASIC与哺乳动物退行性变性蛋白MDEG位于同一脑区，可以直接相互关联。MDEG的免疫沉淀引起ASIC的共沉淀。此外，非洲爪蟾卵母细胞中ASIC和MDEG亚基的共表达产生了一个具有新特性（不同动力学、离子选择性和pH敏感性）的酰胺敏感H+门控Na+通道。此外，MDEG与ASIC亚基突变体的共表达可以产生组成性活性通道，这些通道对Na+完全没有选择性，而K+和H+门控通道与MDEG相比具有显著改变的pH敏感性。这些数据清楚地表明，ASIC和MDEG可以形成具有新性能的异质组装体。异多聚体组装可能用于在不同pH范围内创建多种H+门控阳离子通道，作为神经元酸传感器。
Proton-gated cation channels are acid sensors that are present in both sensory neurons and in neurons of the central nervous system. One of these acid sensing ion channels (ASIC) has been recently cloned. This paper shows that ASIC and the mammalian degenerin MDEG, which are colocalized in the same brain regions, can directly associate with each other. Immunoprecipitation of MDEG causes coprecipitation of ASIC. Moreover, coexpression of ASIC and MDEG subunits in Xenopus oocytes generates an amiloride-sensitive H+-gated Na+ channel with novel properties (different kinetics, ionic selectivity, and pH sensitivity). In addition, coexpression of MDEG with mutants of the ASIC subunit can create constitutively active channels that become completely nonselective for Na+ versus K+ and H+-gated channels that have a drastically altered pH sensitivity compared with MDEG. These data clearly show that ASIC and MDEG can form heteromultimeric assemblies with novel properties. Heteromultimeric assembly is probably used for creating a diversity of H+-gated cation channels acting as neuronal acid sensors in different pH ranges.