Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo
Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo
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DOI：
10.1126/science.276.5312.599
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发表时间：
1997-04-25
期刊：
影响因子：
56.9
通讯作者：
Fischbach, GD
中科院分区：
文献类型：
--
作者：
Sandrock, AW;Dryer, SE;Fischbach, GD
ARIA（乙酰胆碱受体诱导活性）是一种基于其刺激培养的肌管中乙酰胆碱受体（AChR）合成的能力而纯化的蛋白质，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乙酰胆碱受体在突触后膜的神经依赖性积累的重要作用。神经-肌肉突触现在已经在神经调节蛋白缺乏的动物中进行了分析。含有免疫球蛋白样结构域的神经调节蛋白同种型缺失的杂合小鼠是肌无力的。突触后AChR密度显着降低，判断自发性微终板电位和银环蛇毒素结合的平均振幅的减少。另一方面，诱发终板电位的平均振幅没有降低，这是由于每个脉冲释放的量子数增加，这是在其他肌无力状态中观察到的补偿。因此，突触后膜中AChR的密度取决于动物一生中含有免疫球蛋白的神经调节蛋白亚型。
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 end plate 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.