The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABAA receptors
The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABAA receptors
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DOI：
10.1006/mcne.2001.1005
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发表时间：
2001-07-01
影响因子：
3.5
通讯作者：
Moss, SJ
中科院分区：
文献类型：
--
作者：
Kittler, JT;Rostaing, P;Moss, SJ
GABA（A）受体是大脑中快速突触抑制的主要部位，主要由α、β和γ 2亚基组成。受体γ 2亚基与17 kDa微管相关蛋白GABARAP相互作用，但这种相互作用的意义仍然未知。在这里，我们表明，GABARAP，免疫沉淀与GABAA受体，没有发现在抑制性突触内的显着水平，但丰富的高尔基体和突触后池。我们还表明，GABARAP直接结合N-乙基马来酰亚胺敏感因子（NSF），细胞内膜运输事件的关键蛋白质。NSF和GABARAP复合物可以在神经元中检测到，并且这两种蛋白质也共定位于细胞内膜隔室中。总之，我们的观察表明，GABARAP可能发挥作用，在细胞内GABAA受体转运，但不是突触锚定，通过其与NSF相互作用的能力。因此，GABARAP可能在GABA能突触的产生中起重要作用。
GABA(A) receptors the major sites of fast synaptic inhibition in the brain are composed predominately of alpha, beta, and gamma2 subunits. The receptor gamma2 subunit interacts with a 17-kDa microtubule associated protein GABARAP, but the significance of this interaction remains unknown. Here we demonstrate that GABARAP, which immunoprecipitates with GABAA receptors, is not found at significant levels within inhibitory synapses, but is enriched within the Golgi apparatus and postsynaptic cisternae. We also demonstrate that GABARAP binds directly to N-ethylmaleimide-sensitive factor (NSF), a protein critical for intracellular membrane trafficking events. NSF and GABARAP complexes could be detected in neurons and these two proteins also colocalize within intracellular membrane compartments. Together our observations suggest that GABARAP may play a role in intracellular GABAA receptor transport but not synaptic anchoring, via its ability to interact with NSF. GABARAP may therefore have an important role in the production of GABAergic synapses.