Beclin 1 regulates neuronal transforming growth factor-β signaling by mediating recycling of the type I receptor ALK5.
Beclin 1 regulates neuronal transforming growth factor-β signaling by mediating recycling of the type I receptor ALK5.
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DOI：
10.1186/s13024-015-0065-0
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发表时间：
2015-12-21
影响因子：
15.1
通讯作者：
Wyss-Coray T
中科院分区：
文献类型：
--
作者：
O'Brien CE;Bonanno L;Zhang H;Wyss-Coray T
Beclin 1 是多种运输途径的关键调节因子，包括酵母和小胶质细胞中的自噬和受体回收。中枢神经系统中 beclin 1 水平降低会导致神经退行性变，这是由于自噬受损所致。然而，神经元也严重依赖营养因子，并且通过这些途径的信号传导需要营养因子受体的适当运输。我们发现 beclin 1 通过神经保护性 TGF-β 途径调节信号传导。 Beclin 1 是 I 型 TGF-β 受体 ALK5 回收所必需的。我们表明，beclin 1 将逆转录酶招募到 ALK5 并促进其定位到 Rab11+ 内体。 beclin 1 或其结合伙伴 VPS34 和 UVRAG 水平降低会损害 TGF-β 信号传导。这些发现将 beclin 1 确定为通过受体循环的营养信号通路的正调节因子，并表明 beclin 1 水平降低诱导的神经元死亡也可能是由于营养因子信号传导受损所致。本文的在线版本 (doi:10.1186/s13024-015-0065-0) 包含补充材料，可供授权用户使用。
Beclin 1 is a key regulator of multiple trafficking pathways, including autophagy and receptor recycling in yeast and microglia. Decreased beclin 1 levels in the CNS result in neurodegeneration, an effect attributed to impaired autophagy. However, neurons also rely heavily on trophic factors, and signaling through these pathways requires the proper trafficking of trophic factor receptors. We discovered that beclin 1 regulates signaling through the neuroprotective TGF-β pathway. Beclin 1 is required for recycling of the type I TGF-β receptor ALK5. We show that beclin 1 recruits the retromer to ALK5 and facilitates its localization to Rab11+ endosomes. Decreased levels of beclin 1, or its binding partners VPS34 and UVRAG, impair TGF-β signaling. These findings identify beclin 1 as a positive regulator of a trophic signaling pathway via receptor recycling, and suggest that neuronal death induced by decreased beclin 1 levels may also be due to impaired trophic factor signaling. The online version of this article (doi:10.1186/s13024-015-0065-0) contains supplementary material, which is available to authorized users.