A potassium channel-MiRP complex controls neurosensory function in Caenorhabditis elegans
A potassium channel-MiRP complex controls neurosensory function in Caenorhabditis elegans
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DOI：
10.1074/jbc.m212788200
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发表时间：
2003-04-04
影响因子：
4.8
通讯作者：
Sesti, F
中科院分区：
文献类型：
--
作者：
Bianchi, L;Kwok, SM;Sesti, F
MinK相关肽（MiRPs）是与哺乳动物电压门控K+亚基相关的单跨膜蛋白。在这里，我们报告了来自秀丽隐杆线虫的MiRP β亚基MPS-1和电压门控成孔钾亚基KVS-1的克隆和功能表征。MPS-1在化学感觉神经元和机械感觉神经元中表达，并与KVS-1共定位于这些神经元的子集中。通过RNA干扰（RNAi）失活mps-1或kvs-1引起部分重叠的神经元缺陷并导致广谱神经元功能障碍，包括缺陷的趋化性、破坏的机械转导和受损的运动。通过RNAi使一个亚基失活，仅在两种蛋白质共定位的细胞中显著抑制伴侣亚基的表达。MPS-1和KVS-1在哺乳动物细胞中的共表达产生不同于KVS-1电流的钾电流。综合这些数据表明，钾电流构成了C。elegans神经元功能，并揭示了一个具有进化意义统一原则：各种生物体中的钾通道使用MiRPs产生独特的功能，在细节上具有丰富的变化。
MinK-related peptides (MiRPs) are single transmembrane proteins that associate with mammalian voltage-gated K+ subunits. Here we report the cloning and functional characterization of a MiRP beta-subunit, MPS-1, and of a voltage-gated pore-forming potassium subunit, KVS-1, from the nematode Caenorhabditis elegans. mps-1 is expressed in chemosensory and mechanosensory neurons and co-localizes with kvs-1 in a subset of these. Inactivation of either mps-1 or kvs-1 by RNA interference (RNAi) causes partially overlapping neuronal defects and results in broad-spectrum neuronal dysfunction, including defective chemotaxis, disrupted mechanotransduction, and impaired locomotion. Inactivation of one subunit by RNAi dramatically suppresses the expression of the partner subunit only in cells where the two proteins co-localize. Co-expression of MPS-1 and KVS-1 in mammalian cells gives rise to a potassium current distinct from the KVS-1 current. Taken together these data indicate that potassium currents constitute a basic determinant for C. elegans neuronal function and unravel a unifying principle of evolutionary significance: that potassium channels in various organisms use MiRPs to generate uniqueness of function with rich variation in the details.