The promiscuous role of the epsilon subunit in GABAA receptor biogenesis
The promiscuous role of the epsilon subunit in GABAA receptor biogenesis
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DOI：
10.1016/j.mcn.2007.12.011
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Connolly, Christopher N.
中科院分区：
文献类型：
--
作者：
Bollan, Karen A.;Baur, Roland;Connolly, Christopher N.
α 1 β 2 γ 2 α受体的形成表明，α 1 β 2 γ 2受体中的e亚基并不取代单个γ 2亚基。因此，如果要保留五聚体受体结构，e必须取代α和/或β亚基。为了评估α β 1和α β γ 2受体中哪个亚基被取代的可能性，我们分析了α 1、β 2和γ 2亚基的e亚基的组装和功能表达。使用串联的亚基，我们已经确定e能够取代α亚基中的任一个（但不是两个），0亚基中的一个，以及可能的γ 2亚基。然而，e亚基可能对受体功能有贡献的最可能位点似乎是在α β γ 1（ε-β 2-α 1-β 2-γ 2）受体的位置I（替代α 1），或在α β 2（α 1-β 2-α 1-ε-β 2）受体的位置4（替代β 2）。在这两种情况下，似乎只有一个单一的GABA结合位点存在。(c)2007年爱思唯尔公司All rights reserved.
The formation of alpha 1 beta 2 gamma 2 epsilon receptors suggests that the e subunit does not displace the single gamma 2 subunit in alpha 1 beta 2 gamma 2 receptors. Thus, e must replace cc and/or beta subunit(s) if the pentameric receptor structure is to be preserved. To assess the potential for which subunit is replaced in alpha beta epsilon and alpha beta gamma epsilon receptors we analyzed the assembly and functional expression of the e subunit with respect to alpha 1, beta 2 and gamma 2 subunits. Using concatenated subunits, we have determined that e is capable of substituting for either (but not both) of the alpha subunits, one of the 0 subunits, and possibly the gamma 2 subunit. However, the most likely sites at which the e subunit may contribute to receptor function appears to be at position I (replaces alpha 1) in alpha beta gamma epsilon (epsilon-beta 2-alpha 1-beta 2-gamma 2) receptors, or at position 4 (replaces beta 2) in alpha beta epsilon (alpha 1-beta 2-alpha 1-epsilon-beta 2) receptors. In both cases, it appears that only a single GABA binding site is present. (c) 2007 Elsevier Inc. All rights reserved.