Neuronally expressed Ras-family GTPase Di-Ras modulates synaptic activity in Caenorhabditis elegans
Neuronally expressed Ras-family GTPase Di-Ras modulates synaptic activity in Caenorhabditis elegans
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神经元表达的 Ras 家族 GTPase Di-Ras 调节秀丽隐杆线虫的突触活性
DOI：
10.1111/j.1365-2443.2012.01627.x
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发表时间：
2012
期刊：
影响因子：
2.1
通讯作者：
Katada T
中科院分区：
文献类型：
--
作者：
Tada M;Gengyo-Ando K;Kobayashi T;Fukuyama M;Mitani S;Kontani K;Katada T
Ras家族GTP酶调节多种细胞功能，包括细胞生长和分化。Di-Ras属于Ras家族GTP酶的一个独特亚家族，主要在大脑中表达，但Di-Ras在神经系统中的作用仍然完全未知。在这里，我们报告了秀丽隐杆线虫Di-Ras同源物rn-1在神经元细胞中特异性表达，并参与神经肌肉接头的突触功能。drn-1功能的丧失赋予了对乙酰胆碱酯酶抑制剂涕灭威的抗性，并部分抑制了异三聚体G蛋白突变体的涕灭威超敏表型，其中乙酰胆碱释放被上调。drn-1突变体在膜结合的第二信使甘油二酯（DAG）的轴突分布中没有表现出明显的缺陷，DAG是乙酰胆碱释放的关键刺激物。最后，我们已经鉴定了EPAC-1，一种秀丽隐杆线虫Epac同源物，作为DRN-1的结合伴侣。fepac-1缺失突变体表现出涕灭威抗性表型，如drn-1突变体。对drn-1和depac-1的遗传分析表明，它们通过相同的途径控制乙酰胆碱的释放。此外，DRN-1和EPAC-1是共免疫沉淀的。这些发现表明，DRN-1可能与EPAC-1协同作用，调节秀丽隐杆线虫的突触活动。
Ras‐family GTPases regulate a wide variety of cellular functions including cell growth and differentiation. Di‐Ras, which belongs to a distinct subfamily of Ras‐family GTPases, is expressed predominantly in brain, but the role of Di‐Ras in nervous systems remains totally unknown. Here, we report that theCaenorhabditis elegansDi‐Ras homologuedrn‐1is expressed specifically in neuronal cells and involved in synaptic function at neuromuscular junctions. Loss of function ofdrn‐1conferred resistance to the acetylcholinesterase inhibitor aldicarb and partially suppressed the aldicarb‐hypersensitive phenotypes of heterotrimeric G‐protein mutants, in which acetylcholine release is up‐regulated.drn‐1mutants displayed no apparent defects in the axonal distribution of the membrane‐bound second messenger diacylglycerol (DAG), which is a key stimulator of acetylcholine release. Finally, we have identified EPAC‐1, aC. elegansEpac homologue, as a binding partner for DRN‐1. Deletion mutants ofepac‐1displayed an aldicarb‐resistant phenotype asdrn‐1mutants. Genetic analysis ofdrn‐1andepac‐1showed that they acted in the same pathway to control acetylcholine release. Furthermore, DRN‐1 and EPAC‐1 were co‐immunoprecipitated. These findings suggest that DRN‐1 may function cooperatively with EPAC‐1 to modulate synaptic activity inC. elegans.