Small GTPase Rab17 regulates the surface expression of kainate receptors but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal neurons via dendritic trafficking of Syntaxin-4 protein.
Small GTPase Rab17 regulates the surface expression of kainate receptors but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal neurons via dendritic trafficking of Syntaxin-4 protein.
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DOI：
10.1074/jbc.m114.550632
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发表时间：
2014-07-25
期刊：
影响因子：
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通讯作者：
Henley JM
中科院分区：
文献类型：
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作者：
Mori Y;Fukuda M;Henley JM
背景：Rab17 调节海马神经元的树突状运输，但其货物分子尚不清楚。结果：使用 GluK2 和 GluA1 作为标记，我们发现 Rab17 或 Syntaxin-4 敲低会降低 KAR 的树突表面表达，但不会降低 AMPAR。结论：Rab17 通过 Syntaxin-4 的树突运输介导 GluK2 而非 GluA1 的膜插入。意义：Syntaxin-4 专门调节 GluK2 运输。谷氨酸受体对于控制突触传递、突触可塑性和神经元兴奋性至关重要。然而，其贩运背后的许多分子机制仍然难以捉摸。我们之前证明了小 GTPase Rab17 调节海马神经元的树突运输。在这里，我们研究了 Rab17 在 AMPA 受体 (AMPAR) 和红藻氨酸受体 (KAR) 运输中的作用。尽管在基础或化学诱导的长期增强条件下，Rab17 敲低并不影响 AMPAR 亚基 GluA1 的表面表达，但它显着降低了 KAR 亚基 GluK2 的表面表达。 Rab17 与 Syntaxin-4 共定位于体细胞、树突轴、发育中的海马神经元尖端和棘中。 Rab17 敲除导致 Syntaxin-4 从树突重新分布到发育中的海马神经元的轴突中。 Syntaxin-4 敲除减少了 GluK2，但对 GluA1 表面表达没有影响。此外，组成型活性 Rab17 的过表达通过增强 Syntaxin-4 易位到树突来促进 GluK2 的树突表面表达。这些数据表明 Rab17 介导 Syntaxin-4 的树突运输，以选择性调节大鼠海马神经元中含有 GluK2 的 KAR 的树突表面插入。
Background: Rab17 regulates dendritic trafficking in hippocampal neurons, but the cargo molecules are unknown. Results: Using GluK2 and GluA1 as markers, we show that Rab17 or Syntaxin-4 knockdown reduces dendritic surface expression of KARs but not AMPARs. Conclusion: Rab17 mediates membrane insertion of GluK2 but not GluA1 via dendritic trafficking of Syntaxin-4. Significance: Syntaxin-4 specifically regulates GluK2 trafficking. Glutamate receptors are fundamental for control synaptic transmission, synaptic plasticity, and neuronal excitability. However, many of the molecular mechanisms underlying their trafficking remain elusive. We previously demonstrated that the small GTPase Rab17 regulates dendritic trafficking in hippocampal neurons. Here, we investigated the role(s) of Rab17 in AMPA receptor (AMPAR) and kainate receptor (KAR) trafficking. Although Rab17 knockdown did not affect surface expression of the AMPAR subunit GluA1 under basal or chemically induced long term potentiation conditions, it significantly reduced surface expression of the KAR subunit GluK2. Rab17 co-localizes with Syntaxin-4 in the soma, dendritic shaft, the tips of developing hippocampal neurons, and in spines. Rab17 knockdown caused Syntaxin-4 redistribution away from dendrites and into axons in developing hippocampal neurons. Syntaxin-4 knockdown reduced GluK2 but had no effect on GluA1 surface expression. Moreover, overexpression of constitutively active Rab17 promoted dendritic surface expression of GluK2 by enhancing Syntaxin-4 translocation to dendrites. These data suggest that Rab17 mediates the dendritic trafficking of Syntaxin-4 to selectively regulate dendritic surface insertion of GluK2-containing KARs in rat hippocampal neurons.