Beclin 1 regulates neuronal transforming growth factor-β signaling by mediating recycling of the type I receptor ALK5

Molecular Neurodegeneration

Tony Wyss-Coray¹  Hui Zhang¹  Liana Bonanno²  Caitlin E. O’Brien¹ 

[1] Center for Tissue Regeneration, Repair, and Restoration, Veteran Administration Palo Alto Health Care System, Palo Alto, CA 94304, USA;Graduate Program in Neuroscience, Stanford University School of Medicine, Stanford 94305, CA, USA

关键词: Neurodegeneration;    Receptor recycling;    Protein sorting;    ALK5;    TGF-β;    Retromer;    VPS34;    Beclin 1;   

Others  :  1235066
DOI  :  10.1186/s13024-015-0065-0

 received in 2015-07-30, accepted in 2015-12-10,  发布年份 2015

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2015 O’Brien et al.

【 图 表 】

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