Regulation of nicotinic receptor trafficking by the transmembrane Golgi protein UNC-50
Regulation of nicotinic receptor trafficking by the transmembrane Golgi protein UNC-50
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DOI：
10.1038/sj.emboj.7601858
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发表时间：
2007-10-17
期刊：
影响因子：
11.4
通讯作者：
Bessereau, Jean-Louis
中科院分区：
文献类型：
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作者：
Eimer, Stefan;Gottschalk, Alexander;Bessereau, Jean-Louis
烟碱型乙酰胆碱受体(AChRs)是五聚体配体门控离子通道，在神经肌肉接头(NMJ)介导快速突触传递。在内质网(ER)组装后，AChRs必须通过分泌装置运输到质膜。人们对调节这种运输的特定分子知之甚少。在这里，我们确定了秀丽隐杆线虫中组装的尼古丁AChRs的亚型特异性运输所需的基因。UNC-50编码一种进化上保守的完整膜蛋白，定位于高尔基体。在没有UNC-50的情况下，存在于体壁肌肉中的AChRs的一部分被分选到溶酶体系统并被降解。然而，在UNC-50突变体中，第二种AChR类型和在同一肌肉细胞中表达的GABA亲离子受体的运输不受影响。这些结果表明，除了内质网质量控制外，在高尔基体系统中，组装的AChR是通过一种机制来分类的，该机制以亚型特异性的方式控制细胞表面AChR的数量。
Nicotinic acetylcholine receptors (AChRs) are pentameric ligand-gated ion channels that mediate fast synaptic transmission at the neuromuscular junction (NMJ). After assembly in the endoplasmic reticulum ( ER), AChRs must be transported to the plasma membrane through the secretory apparatus. Little is known about specific molecules that mediate this transport. Here we identify a gene that is required for subtype-specific trafficking of assembled nicotinic AChRs in Caenorhabditis elegans. unc-50 encodes an evolutionarily conserved integral membrane protein that localizes to the Golgi apparatus. In the absence of UNC-50, a subset of AChRs present in body-wall muscle are sorted to the lysosomal system and degraded. However, the trafficking of a second AChR type and of GABA ionotropic receptors expressed in the same muscle cells is not affected in unc-50 mutants. These results suggest that, in addition to ER quality control, assembled AChRs are sorted within the Golgi system by a mechanism that controls the amount of cell-surface AChRs in a subtype-specific way.