Identification of 70 amino acids important for GABA(C) receptor rho1 subunit assembly.
Identification of 70 amino acids important for GABA(C) receptor rho1 subunit assembly.
复制标题
鉴定对 GABA(C) 受体 rho1 亚基组装重要的 70 个氨基酸。
DOI：
10.1016/s0006-8993(99)02008-9
复制
发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Cutting,GR
中科院分区：
文献类型：
--
作者：
Enz,R;Cutting,GR
γ-氨基丁酸（γ-Aminobutyric acid，GABA）是哺乳动物中枢神经系统中最重要的抑制性神经递质，至少可控制GABAA、GABAB和GABAC三种受体。越来越多的证据表明GABA C受体仅由ρ亚基组成。已显示ρ亚基的N-末端一半介导同源和异源寡聚GABAC受体的形成。在这项研究中，我们寻找特定的序列内的N-末端的ρ1亚基参与组装过程。通过删除先前显示破坏ρ1和ρ2装配的嵌合ρ1β1亚基的逐渐增大的区域，将装配序列定位于128个氨基酸的区域。为了证实这一观察结果，检测了一系列含有ρ1 N端不同区域的GABA A受体β亚基嵌合体对ρ1和ρ2亚基组装成功能性GABA受体的干扰。将128个氨基酸区域内的70个残基转移到β1亚基上产生了一种嵌合体，该嵌合体破坏了ρ1而不是ρ2组装成功能性受体。这些观察结果精确地定位了参与ρ1亚基组装的信号，并表明对于ρ1同源寡聚体和ρ1/ρ2异源寡聚体GABAC受体的形成存在不同的信号。
γ-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the mammalian central nervous system and gates at least three subclasses of receptors, termed GABAA, GABABand GABAC. Accumulating evidence indicates that GABACreceptors are composed exclusively of ρ subunits. The N-terminal half of the ρ subunits has been shown to mediate formation of homo- and heterooligomeric GABACreceptors. In this study, we searched for specific sequences within the N-terminus of the ρ1 subunit involved in the assembly process. Assembly sequences were localized to a 128-amino acid region by deletion of progressively larger regions of a chimeric ρ1β1 subunit previously shown to disrupt ρ1 and ρ2 assembly. To confirm this observation, a series of GABAAreceptor β subunit chimeras containing different regions of the ρ1 N-terminus were tested for interference with ρ1 and ρ2 subunit assembly into functional GABA receptors. Transfer of 70 residues within the 128 amino acid region to the β1 subunit created a chimera that disrupted ρ1, but not ρ2, assembly into functional receptors. These observations refine the location of signals involved in ρ1 subunit assembly, and suggest that different signals exist for the formation of ρ1 homooligomeric and ρ1/ρ2 heterooligomeric GABACreceptors.