Neuronal cotransport of glycine receptor and the scaffold protein gephyrin.

Neuronal cotransport of glycine receptor and the scaffold protein gephyrin.
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DOI:
10.1083/jcb.200506066
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发表时间:
2006-01-30
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Kneussel M
Kneussel M
中科院分区:
其他
文献类型:
--
作者:
Maas C;Tagnaouti N;Loebrich S;Behrend B;Lappe-Siefke C;Kneussel M

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抑制性突触的突触后受体支架形成和重塑的动力学仍然很大程度上是未知的。Gephyrin是一种多聚支架蛋白,与细胞骨架元件相互作用,稳定突触后抑制位点的甘氨酸受体(GlyRs)和γ-氨基丁酸a受体的个体亚型。我们报告了随着时间的推移gephyrin运输包的细胞内迁移。格菲林单位在几分钟内进入和退出活跃的突触。除了先前报道的GlyR-gephyrin在质膜上的相互作用外,我们还从囊泡部分中发现了两种蛋白质的共沉淀和共免疫沉淀。此外,GlyR和gephyrin在神经元树突内共同运输,并进一步与动力蛋白运动复合物共免疫沉淀和共定位。因此,动力蛋白功能或动力蛋白与格菲林相互作用的阻断,以及微管的解聚,都会干扰格菲林逆行募集。我们的数据表明GlyR-gephyrin-dynein运输复合物,并支持gephyrin-motor相互作用有助于突触后GlyRs的动态和活动依赖性重排的概念,这一过程被认为是突触强度调节的基础。
The dynamics of postsynaptic receptor scaffold formation and remodeling at inhibitory synapses remain largely unknown. Gephyrin, which is a multimeric scaffold protein, interacts with cytoskeletal elements and stabilizes glycine receptors (GlyRs) and individual subtypes of γ-aminobutyric acid A receptors at inhibitory postsynaptic sites. We report intracellular mobility of gephyrin transports packets over time. Gephyrin units enter and exit active synapses within several minutes. In addition to previous reports of GlyR–gephyrin interactions at plasma membranes, we show cosedimentation and coimmunoprecipitation of both proteins from vesicular fractions. Moreover, GlyR and gephyrin are cotransported within neuronal dendrites and further coimmunoprecipitate and colocalize with the dynein motor complex. As a result, the blockade of dynein function or dynein–gephyrin interaction, as well as the depolymerization of microtubules, interferes with retrograde gephyrin recruitment. Our data suggest a GlyR–gephyrin–dynein transport complex and support the concept that gephyrin–motor interactions contribute to the dynamic and activity-dependent rearrangement of postsynaptic GlyRs, a process thought to underlie the regulation of synaptic strength.
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影响因子: --
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