A single immunoglobulin-domain protein required for clustering acetylcholine receptors in C. elegans
A single immunoglobulin-domain protein required for clustering acetylcholine receptors in C. elegans
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DOI：
10.1038/emboj.2010.355
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发表时间：
2011-02-16
期刊：
影响因子：
11.4
通讯作者：
Bessereau, Jean-Louis
中科院分区：
文献类型：
--
作者：
Rapti, Georgia;Richmond, Janet;Bessereau, Jean-Louis
在秀丽隐杆线虫神经肌肉连接处（NMJs），左旋咪唑敏感乙酰胆碱受体（l - achr）的突触聚集依赖于突触间隙中组装的细胞外支架。它涉及分泌蛋白LEV-9和跨膜蛋白LEV-10的外畴，两者都是由肌肉细胞表达的。l - achr， LEV-9和LEV-10是物理复合物的一部分，定位于NMJs，但其成分都不独立定位于突触。在筛选对胆碱能激动剂左旋咪唑部分耐药的突变体时，我们发现了oig-4，它编码一种含有单一免疫球蛋白结构域的小蛋白。OIG-4蛋白由肌肉细胞分泌，与L-AChR/LEV-9/LEV-10复合物相互作用。去除OIG-4会破坏复合物的稳定性，并导致突触上L-AChR簇的丢失。有趣的是，OIG-4部分定位于NMJs，独立于LEV-9和LEV-10，从而在l - achr相关支架和局部突触信号之间提供了潜在的联系。这些结果为免疫球蛋白超家族增加了一个新的范例，因为OIG-4是一种独立于突触形成的聚类嗜离子受体所需的分泌蛋白。EMBO杂志（2011）30,706-718。doi: 10.1038 / emboj.2010.355;2011年1月21日在线发布
At Caenorhabditis elegans neuromuscular junctions (NMJs), synaptic clustering of the levamisole-sensitive acetylcholine receptors (L-AChRs) relies on an extracellular scaffold assembled in the synaptic cleft. It involves the secreted protein LEV-9 and the ectodomain of the transmembrane protein LEV-10, which are both expressed by muscle cells. L-AChRs, LEV-9 and LEV-10 are part of a physical complex, which localizes at NMJs, yet none of its components localizes independently at synapses. In a screen for mutants partially resistant to the cholinergic agonist levamisole, we identified oig-4, which encodes a small protein containing a single immunoglobulin domain. The OIG-4 protein is secreted by muscle cells and physically interacts with the L-AChR/LEV-9/LEV-10 complex. Removal of OIG-4 destabilizes the complex and causes a loss of L-AChR clusters at the synapse. Interestingly, OIG-4 partially localizes at NMJs independently of LEV-9 and LEV-10, thus providing a potential link between the L-AChR-associated scaffold and local synaptic cues. These results add a novel paradigm for the immunoglobulin super-family as OIG-4 is a secreted protein required for clustering ionotropic receptors independently of synapse formation. The EMBO Journal (2011) 30, 706-718. doi:10.1038/emboj.2010.355; Published online 21 January 2011