Ericksen Spencer S, Boileau Andrew J
Department of Physiology, University of Wisconsin-Madison, Madison, WI, USA.
Mol Neurobiol. 2007 Feb;35(1):113-28.
Receptor subunits in the Cys-loop superfamily assemble to form channels as homopentamers or heteropentamers, expanding functional diversity through modularity. Expression of two or more compatible subunit types can lead to various receptor assemblies or subtypes. However, what may be good for diversity in vivo may be undesirable for the bench scientist, because we often wish to reduce our analyses to a single receptor subtype. By linking two or more subunits, creating tandems or concatamers, we can control stoichiometry and limit expression to exactly one receptor subtype. In this fashion, receptors with mixed subunit subtypes and heterozygous mutations can be separated from a mixture and can be described in detail. However, several recent studies have shown that this may be more easily conceived than accomplished, because several unforeseen problems have arisen. Concatamers can degrade, linkers can sometimes be clipped after or during translation, and one subunit may "loop out" or even become part of a second (now linked) pentamer with different characteristics. Some strategies have been developed to overcome these drawbacks, and the resultant new information that has begun to emerge has revitalized the study of these receptors in heterologous expression systems.
半胱氨酸环超家族中的受体亚基组装形成同五聚体或异五聚体通道，通过模块化扩展功能多样性。两种或更多种兼容亚基类型的表达可导致各种受体组装体或亚型。然而，对体内多样性有益的因素对实验科学家来说可能并不理想，因为我们常常希望将分析局限于单一受体亚型。通过连接两个或更多个亚基，形成串联体或拼接体，我们可以控制化学计量，并将表达精确限制为一种受体亚型。通过这种方式，具有混合亚基亚型和杂合突变的受体可以从混合物中分离出来，并能得到详细描述。然而，最近的几项研究表明，这可能说起来容易做起来难，因为出现了一些意想不到的问题。拼接体可能会降解，连接子有时会在翻译后或翻译过程中被剪切，并且一个亚基可能会“环出”，甚至成为具有不同特性的第二个（现在已连接的）五聚体的一部分。已经开发出一些策略来克服这些缺点，并且由此开始出现的新信息为异源表达系统中这些受体的研究注入了新的活力。
