Leibniz Institut für Altersforschung-Fritz Lipmann Institut, 07743 Jena, Germany.
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):621-5. doi: 10.1073/pnas.1001624108. Epub 2010 Dec 27.
The nicotinic acetylcholine receptor of skeletal muscle is composed of five subunits that are assembled in a stepwise manner. Quality control mechanisms ensure that only fully assembled receptors reach the cell surface. Here, we show that Rer1, a putative Golgi-ER retrieval receptor, is involved in the biogenesis of acetylcholine receptors. Rer1 is expressed in the early secretory pathway in the myoblast line C2C12 and in mouse skeletal muscle, and up-regulated during myogenesis. Upon down-regulation of Rer1 in C2C12 cells, unassembled acetylcholine receptor α-subunits escape from the ER and are transported to the plasma membrane and lysosomes, where they are degraded. As a result, the amount of fully assembled receptor at the cell surface is reduced. In vivo Rer1 knockdown and genetic inactivation of one Rer1 allele lead to significantly smaller neuromuscular junctions in mice. Our data show that Rer1 is a functionally important unique factor that controls surface expression of muscle acetylcholine receptors by localizing unassembled α-subunits to the early secretory pathway.
骨骼肌中的烟碱型乙酰胆碱受体由五个亚基组成，这些亚基以逐步的方式组装。质量控制机制确保只有完全组装的受体才能到达细胞表面。在这里，我们表明，假定的高尔基体-内质网回收受体 Rer1 参与乙酰胆碱受体的生物发生。Rer1 在肌母细胞系 C2C12 和小鼠骨骼肌中的早期分泌途径中表达，并在肌发生过程中上调。在 C2C12 细胞中下调 Rer1 后，未组装的乙酰胆碱受体 α 亚基从 ER 逃逸，并被转运到质膜和溶酶体，在那里被降解。结果，细胞表面完全组装的受体数量减少。体内 Rer1 敲低和一个 Rer1 等位基因的遗传失活导致小鼠的神经肌肉接头明显变小。我们的数据表明，Rer1 是一种功能上重要的独特因子，通过将未组装的 α 亚基定位到早期分泌途径来控制肌肉乙酰胆碱受体的表面表达。
