Sandrock A W, Dryer S E, Rosen K M, Gozani S N, Kramer R, Theill L E, Fischbach G D
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Science. 1997 Apr 25;276(5312):599-603. doi: 10.1126/science.276.5312.599.
ARIA (for acetylcholine receptor-inducing activity), a protein purified on the basis of its ability to stimulate acetylcholine receptor (AChR) synthesis in cultured myotubes, is a member of the neuregulin family and is present at motor endplates. This suggests an important role for neuregulins in mediating the nerve-dependent accumulation of AChRs in the postsynaptic membrane. Nerve-muscle synapses have now been analyzed in neuregulin-deficient animals. Mice that are heterozygous for the deletion of neuregulin isoforms containing an immunoglobulin-like domain are myasthenic. Postsynaptic AChR density is significantly reduced, as judged by the decrease in the mean amplitude of spontaneous miniature endplate potentials and bungarotoxin binding. On the other hand, the mean amplitude of evoked endplate potentials was not decreased, due to an increase in the number of quanta released per impulse, a compensation that has been observed in other myasthenic states. Thus, the density of AChRs in the postsynaptic membrane depends on immunoglobulin-containing neuregulin isoforms throughout the life of the animal.
ARIA（乙酰胆碱受体诱导活性蛋白）是一种基于其在培养的肌管中刺激乙酰胆碱受体（AChR）合成的能力而纯化得到的蛋白质，它是神经调节蛋白家族的成员，存在于运动终板。这表明神经调节蛋白在介导突触后膜中AChR的神经依赖性积累方面具有重要作用。目前已经对神经调节蛋白缺陷动物的神经肌肉突触进行了分析。缺失含有免疫球蛋白样结构域的神经调节蛋白亚型的杂合小鼠患有肌无力。根据自发微小终板电位的平均幅度降低和银环蛇毒素结合情况判断，突触后AChR密度显著降低。另一方面，诱发终板电位的平均幅度并未降低，这是由于每个冲动释放的量子数量增加，这种补偿现象在其他肌无力状态中也有观察到。因此，在动物的整个生命周期中，突触后膜中AChR的密度取决于含免疫球蛋白的神经调节蛋白亚型。
