Length of the TM3-4 loop of the glycine receptor modulates receptor desensitization
Length of the TM3-4 loop of the glycine receptor modulates receptor desensitization
复制标题
甘氨酸受体TM3-4环的长度调节受体脱敏
DOI：
10.1016/j.neulet.2015.06.017
复制
发表时间：
2015
影响因子：
2.5
通讯作者：
Villmann C
中科院分区：
文献类型：
--
作者：
Langlhofer G;Janzen D;Meiselbach H;Villmann C
最近对甘氨酸受体生物发生和功能机制重要的分子决定因素的研究表明跨膜结构域 (TM) 3 和 4 之间的细胞内环内碱性残基的重要作用。我们利用转染细胞系中的表达，研究了环长度和环交换与人甘氨酸受体 α1 的基本延伸 318RRKRR 和 385KKIDK 的存在或不存在相结合的作用。 Cys环受体家族成员之间大细胞内环的交换已被证明可以保持宿主受体的功能。在这里，通过删除甘氨酸受体α1的胞内环，插入来自紫色胶杆菌的原核Cys环受体的环，在胞内结构域的N端和C端部分留下或不留下基本延伸来生成构建体。所有受体构建体均在细胞表面表达，其中删除甘氨酸受体α1 TM3-4环的构建体的表达显着最低，除了相邻的两个基本延伸段之外。抑制性甘氨酸受体嵌合体的功能通过转染细胞的全细胞记录得到证实。缺乏基本伸展的嵌合体会导致无功能。受体脱敏分析表明，两个基本延伸的接近导致了大部分脱敏电流。我们得出的结论是，TM3-4 环长度对于甘氨酸受体 α1 脱敏至关重要，并且两个基本片段的直接邻域会将受体特性从非脱敏变为脱敏。
Recent studies on the molecular determinants important for glycine receptor biogenesis and function mechanisms indicate an important role of basic residues within the intracellular loop between transmembrane domains (TM) 3 and 4. We investigate the role of loop length and loop exchange in combination with the presence or absence of basic stretches318RRKRR and385KKIDK of the human glycine receptor α1 using expression in transfected cell lines. Exchanges of the large intracellular loop between members of the Cys-loop receptor family have been shown to keep functionality of the host receptor. Here, constructs were generated with deletion of the intracellular loop of the glycine receptor α1, insertion of the loop from the prokaryotic Cys-loop receptor ofGloeobacter violaceusboth with and without leaving the basic stretches at the N-terminal and C-terminal part of the intracellular domain. All receptor constructs were expressed at the cell surface with the significantly lowest expression of the construct with a deletion of the glycine receptor α1 TM3-4 loop, except the two basic stretches adjoined. Functionality of the inhibitory glycine receptor chimeras was demonstrated with whole cell recordings from transfected cells. Chimeras lacking the basic stretches result in non-functionality. An analysis of receptor desensitization demonstrated that close proximity of both basic stretches resulted in large fractions of desensitizing currents. We conclude that the TM3-4 loop length is critical for glycine receptor α1 desensitization and a direct neighborhood of both basic stretches changes receptor properties from non-desensitizing to desensitizing.
登录
查看更多内容
影响因子：
64.8
作者：
Althoff, Thorsten;Hibbs, Ryan E.;Banerjee, Surajit;Gouaux, Eric
通讯作者：
Gouaux, Eric
TM3-4 环子结构域对于独立结构域功能重建甘氨酸受体的重要性*
DOI：
10.1074/jbc.m112.376053
发表时间：
2012
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Unterer B;Becker CM;Villmann C
通讯作者：
Villmann C
通过独立表达的 C 端结构域对甘氨酸受体亚基突变体 Glra1spd-ot 进行功能互补
DOI：
10.1523/jneurosci.4400-08.2009
发表时间：
2009
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
C. Villmann;Jana Oertel;Zhan;M. Hollmann;R. Sprengel;Kristina Becker;H. Breitinger;C. Becker
通讯作者：
C. Becker
单表达甘氨酸受体结构域重建功能离子通道，无亚基特异性脱敏行为*
DOI：
10.1074/jbc.m114.559138
发表时间：
2014
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Meiselbach;N. Vogel;G. Langlhofer;S. Stangl;B. Schleyer;L. Bahnassawy;H. Sticht;H.G. Breitinger;C.M. Becker;C. Villmann
通讯作者：
C. Villmann