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首页> 外文期刊>Brain research >The Vps52 subunit of the GARP and EARP complexes is a novel Arf6-interacting protein that negatively regulates neurite outgrowth of hippocampal neurons
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The Vps52 subunit of the GARP and EARP complexes is a novel Arf6-interacting protein that negatively regulates neurite outgrowth of hippocampal neurons

机译：GARP和EARP复合物的VPS52亚基是一种新的ARF6 - 相互作用的蛋白，负面调节海马神经元的神经突生长

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摘要

ADP ribosylation factor 6 (Arf6) is a small GTP-binding protein implicated in neuronal morphogenesis through endosomal trafficking and actin remodeling. In this study, we identified Vps52, a core subunit of the Golgi-associated retrograde protein (GARP) and endosome-associated recycling protein (EARP) complexes, as a novel Arf6-binding protein by yeast two-hybrid screening. Vps52 interacted specifically with GTP-bound Arf6 among the Arf family. Immunohistochemical analyses of hippocampal pyramidal cells revealed that fine punctate immunolabeling for Vps52 was distributed throughout neuronal compartments, most densely in the cell body and dendritic shafts, and was largely associated with trans-Golgi network and vesicular endomembranes. In cultured hippocampal neurons, knockdown of Vps52 increased total length of axons and dendrites; these phenotypes were completely restored by co-expression of shRNA-resistant full-length Vps52. However, co-expression of a Vps52 mutant lacking the ability to interact with Arf6 restored only the Vps52-knockdown phenotype of the dendritic length. The present findings suggest that Vps52 is a novel Arf6-interacting protein that regulates neurite outgrowth in hippocampal neurons.
机译：ADP核糖基化因子6（ARF6）是一种小的GTP结合蛋白，其通过内体贩运和肌动蛋白重塑具有神经元形态发生。在该研究中，我们鉴定了Volgi相关的逆行蛋白（Garp）和内体相关的回收蛋白（EARP）复合物的核心亚基，作为通过酵母双杂交筛选的新型ARF6结合蛋白。 VPS52专门与ARF系列中的GTP结合的ARF6进行互动。海马金字塔型细胞的免疫组织化学分析显示，在整个神经元隔室中分布在细胞体和树突轴上的细斑块免疫标记分布在整个神经元隔室中，并且在很大程度上与Trans-GoLgi网络和凹凸内膜有关。在培养的海马神经元中，VPS52的敲低增加了轴突和树枝状的总长度;通过Chna抗性全长VPS52的共表达完全恢复这些表型。然而，缺乏与ARF6相互作用的能力的VPS52突变体的共表达仅恢复树枝状长度的VPS52敲低表型。本研究结果表明，VPS52是一种新的ARF6 - 相互作用蛋白，可调节海马神经元的神经突生长。

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