Phillips W D, Merlie J P
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis MO 63110.
Bioessays. 1992 Oct;14(10):671-9. doi: 10.1002/bies.950141005.
The developing neuromuscular junction has provided an important paradigm for studying synapse formation. An outstanding feature of neuromuscular differentiation is the aggregation of acetylcholine receptors (AChRs) at high density in the postsynaptic membrane. While AChR aggregation is generally believed to be induced by the nerve, the mechanisms underlying aggregation remain to be clarified. A 43-kD protein (43k) normally associated with the cytoplasmic aspect of AChR clusters has long been suspected of immobilizing AChRs by linking them to the cytoskeleton. In recent studies, the AChR clustering activity of 43k has, at last, been demonstrated by expressing recombinant AChR and 43k in non-muscle cells. Mutagenesis of 43k has revealed distinct domains within the primary structure which may be responsible for plasma membrane targeting and AChR binding. Other lines of study have provided clues as to how nerve-derived (extracellular) AChR-cluster inducing factors such as agrin might activate 43k-driven postsynaptic membrane specialization.
发育中的神经肌肉接头为研究突触形成提供了一个重要的范例。神经肌肉分化的一个显著特征是乙酰胆碱受体（AChRs）在突触后膜上高密度聚集。虽然一般认为AChR聚集是由神经诱导的，但其聚集的潜在机制仍有待阐明。一种通常与AChR簇的细胞质面相关的43-kD蛋白（43k）长期以来一直被怀疑通过将AChRs与细胞骨架相连来使其固定。在最近的研究中，通过在非肌肉细胞中表达重组AChR和43k，最终证明了43k的AChR聚集活性。43k的诱变揭示了一级结构中可能负责质膜靶向和AChR结合的不同结构域。其他研究方向为神经源性（细胞外）AChR簇诱导因子（如聚集蛋白）如何激活43k驱动的突触后膜特化提供了线索。
