Acetylcholine receptor clustering is triggered by a change in the density of a nonreceptor molecule.
Acetylcholine receptor clustering is triggered by a change in the density of a nonreceptor molecule.
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乙酰胆碱受体聚类是由非受体分子密度变化触发的。
DOI：
10.1083/jcb.111.5.2029
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发表时间：
1990-11
期刊：
影响因子：
--
通讯作者：
Fraser SE
中科院分区：
文献类型：
--
作者：
Stollberg J;Fraser SE
乙酰胆碱受体在突触发生过程中聚集在神经肌肉接头处，至少部分是通过广泛表达的受体的横向迁移。我们之前已经表明，电场启动特定的受体聚集事件，该事件依赖于神经肌肉细胞培养物中的横向迁移（Stollberg，J.和S.E.Fraser.1988.J.Cell Biol.107：1397-1408）。随后对该模型系统的研究排除了通过将受体密度增加到超过临界阈值而触发聚类事件的可能性(Stollberg, J., and S. E. Fraser. 1990. J. Neurosci. 10:247-255)。这留下了两种可能性：聚类事件可能由场引起的其他分子密度变化触发，或者由膜电压敏感机制（例如电压门控钙信号）触发。电迁移是一个缓慢的线性过程，而电压敏感机制以快速的非线性方式响应。因此，这两种可能性对响应脉冲或交变电场的受体聚集行为做出了不同的预测。在目前的工作中，我们研究了亚细胞钙分布以及受体聚类，以响应这些场。亚细胞钙分布被量化并发现与预测的非线性响应一致。然而，受体聚类的行为符合线性响应的预测，与电迁移假设一致。实验表明，钙的局部增加，或者更一般地说，电压敏感机制，不足以触发受体聚集，也可能没有必要。缓慢交变电场的实验证实了这样的观点，即乙酰胆碱受体的聚集是由某些非受体分子密度的局部变化引发的。
Acetylcholine receptors become clustered at the neuromuscular junction during synaptogenesis, at least in part via lateral migration of diffusely expressed receptors. We have shown previously that electric fields initiate a specific receptor clustering event which is dependent on lateral migration in aneural muscle cell cultures (Stollberg, J., and S. E. Fraser. 1988. J. Cell Biol. 107:1397-1408). Subsequent work with this model system ruled out the possibility that the clustering event was triggered by increasing the receptor density beyond a critical threshold (Stollberg, J., and S. E. Fraser. 1990. J. Neurosci. 10:247-255). This leaves two possibilities: the clustering event could be triggered by the field-induced change in the density of some other molecule, or by a membrane voltage-sensitive mechanism (e.g., a voltage- gated calcium signal). Electromigration is a slow, linear process, while voltage-sensitive mechanisms respond in a rapid, nonlinear fashion. Because of this the two possibilities make different predictions about receptor clustering behavior in response to pulsed or alternating electric fields. In the present work we have studied subcellular calcium distributions, as well as receptor clustering, in response to such fields. Subcellular calcium distributions were quantified and found to be consistent with the predicted nonlinear response. Receptor clustering, however, behaves in accordance with the predictions of a linear response, consistent with the electromigration hypothesis. The experiments demonstrate that a local increase in calcium, or, more generally, a voltage-sensitive mechanism, is not sufficient and probably not necessary to trigger receptor clustering. Experiments with slowly alternating electric fields confirm the view that the clustering of acetylcholine receptors is initiated by a local change in the density of some non-receptor molecule.