Defective neuromuscular synaptogenesis in agrin-deficient mutant mice
Defective neuromuscular synaptogenesis in agrin-deficient mutant mice
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DOI：
10.1016/s0092-8674(00)81253-2
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发表时间：
1996-05-17
期刊：
影响因子：
64.5
通讯作者：
Sanes, JR
中科院分区：
文献类型：
--
作者：
Gautam, M;Noakes, PG;Sanes, JR
在神经肌肉突触形成过程中，运动轴突诱导乙酰胆碱受体（AChRs）在肌纤维膜上聚集。蛋白聚集蛋白，最初从突触间隙的基底层中分离，由运动神经元合成和分泌，并触发培养的肌管上AChR簇的形成。我们在这里表明，突触后乙酰胆碱受体聚集体的数量，大小和密度显着减少，在肌肉的聚集蛋白缺陷的突变小鼠。这些结果支持了聚集蛋白是突触后分化的重要组织者的假设。然而，一些突触后分化确实发生在突变体中，这表明存在第二个神经源性突触组织信号。此外，我们表明，肌内神经分支和突触前分化是异常的突变体，表型，这可能反映了一个独特的影响聚集蛋白或受损的逆行信号从一个有缺陷的突触后装置。
During neuromuscular synapse formation, motor axons induce clustering of acetylcholine receptors (AChRs) in the muscle fiber membrane. The protein agrin, originally isolated from the basal lamina of the synaptic cleft, is synthesized and secreted by motoneurons and triggers formation of AChR clusters on cultured myotubes. We show here that postsynaptic AChR aggregates are markedly reduced in number, size, and density in muscles of agrin-deficient mutant mice. These results support the hypothesis that agrin is a critical organizer of postsynaptic differentiation. However, some postsynaptic differentiation does occur in the mutant, suggesting the existence of a second nerve-derived synaptic organizing signal. In addition, we show that intramuscular nerve branching and presynaptic differentiation are abnormal in the mutant, phenotypes which may reflect either a distinct effect of agrin or impaired retrograde signaling from a defective postsynaptic apparatus.