Mayer Mark L, Armstrong Neali
Laboratory of Cellular and Molecular Neurophysiology, Building 36, Room 2B28, NICHD, NIH, DHHS, Bethesda, Maryland 20892, USA.
Annu Rev Physiol. 2004;66:161-81. doi: 10.1146/annurev.physiol.66.050802.084104.
A vast number of proteins are involved in synaptic function. Many have been cloned and their functional role defined with varying degrees of success, but their number and complexity currently defy any molecular understanding of the physiology of synapses. A beacon of success in this medieval era of synaptic biology is an emerging understanding of the mechanisms underlying the activity of the neurotransmitter receptors for glutamate. Largely as a result of structural studies performed in the past three years we now have a mechanistic explanation for the activation of channel gating by agonists and partial agonists; the process of desensitization, and its block by allosteric modulators, is also mostly explained; and the basis of receptor subtype selectivity is emerging with clarity as more and more structures are solved. In the space of months we have gone from cartoons of postulated mechanisms to hard fact. It is anticipated that this level of understanding will emerge for other synaptic proteins in the coming decade.
大量蛋白质参与突触功能。许多蛋白质已被克隆,其功能作用也得到了不同程度的明确,但目前它们的数量和复杂性使得人们难以从分子层面理解突触的生理学机制。在这个突触生物学的“中世纪”时代,一个成功的标志是对谷氨酸神经递质受体活性的潜在机制有了新的认识。在很大程度上,由于过去三年进行的结构研究,我们现在对激动剂和部分激动剂激活通道门控的机制有了一个机械性的解释;脱敏过程及其被变构调节剂阻断的情况也大多得到了解释;随着越来越多的结构被解析,受体亚型选择性的基础也越来越清晰。在短短几个月的时间里,我们已经从假定机制的示意图走向了确凿的事实。预计在未来十年,对于其他突触蛋白也会出现这种程度的理解。