Identification and characterisation of a Maf1/Macoco protein complex that interacts with GABAA receptors in neurons.

Identification and characterisation of a Maf1/Macoco protein complex that interacts with GABAA receptors in neurons.
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DOI:
10.1016/j.mcn.2010.04.004
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发表时间:
2010-08
影响因子:
3.5
通讯作者:
Kittler, Josef T.
Kittler, Josef T.
中科院分区:
医学3区
文献类型:
--
作者:
Smith, Katharine R.;Oliver, Peter L.;Lumb, Michael J.;Arancibia-Carcamo, I. Lorena;Revilla-Sanchez, Raquel;Brandon, Nicholas J.;Moss, Stephen J.;Kittler, Josef T.

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哺乳动物神经系统中的大多数快速抑制性突触传递由GABAA受体(GABAARs)介导。在这里,我们报告了蛋白Maf 1和GABAAR β亚基胞内结构域之间的新的相互作用。我们发现Maf 1在大脑中高度表达,并在海马和皮质中富集。在异源细胞和神经元中,我们显示Maf 1与GABAAR在细胞内隔室和细胞表面共定位。在神经元中,Maf 1被发现定位于树突的细胞质中,与GABAAR和抑制性突触部分重叠,并且另外在神经元核中富集。我们还报告说,Maf 1相互作用与一种新的卷曲螺旋结构域包含蛋白质,我们称之为Macoco(Maf 1相互作用卷曲螺旋蛋白)。与Maf 1一样,Macoco也可以定位于抑制性突触,并直接与GABAAR相互作用。在神经元中表达Macoco增加表面GABAAR水平。我们的研究结果表明,Maf 1和Macoco是新的GABAAR相互作用的蛋白质重要的GABAAR表面表达和GABAAR信号在大脑中的调节。
The majority of fast inhibitory synaptic transmission in the mammalian nervous system is mediated by GABAA receptors (GABAARs). Here we report a novel interaction between the protein Maf1 and GABAAR β-subunit intracellular domains. We find Maf1 to be highly expressed in brain and enriched in the hippocampus and cortex. In heterologous cells and neurons we show Maf1 co-localises with GABAARs in intracellular compartments and at the cell surface. In neurons, Maf1 is found localised in the cytoplasm in dendrites, partially overlapping with GABAARs and inhibitory synapses and in addition is enriched in the neuronal nucleus. We also report that Maf1 interacts with a novel coiled-coil domain containing protein that we have called Macoco (for Maf1 interacting coiled-coil protein). Like Maf1, Macoco can also be found localised to inhibitory synapses and directly interacts with GABAARs. Expressing Macoco in neurons increases surface GABAAR levels. Our results suggest that Maf1 and Macoco are novel GABAAR interacting proteins important for regulating GABAAR surface expression and GABAAR signalling in the brain.
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