【原】TMEM55B有助于溶酶体稳态和氨基酸诱导的mTORC1激活

 TMEM55B contributes to lysosomal homeostasis and amino  acid–induced mTORC1 activation

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|核心内容：

哺乳动物雷帕霉素复合物1的机制靶点(mTORC1)对生长因子和营养可利用性有反应。

氨基酸诱导mTORC1被招募到溶酶体膜并进而被激活，但这种激活的分子机制尚不清楚。

我们现在已经研究了TMEM55B的作用，这是一种分子功能未知的溶酶体蛋白，根据蛋白质组学和免疫荧光分析的结果显示，TMEM55B与许多参与mTORC1激活的蛋白质相互作用，包括液泡型质子ATP酶(V-atp酶)和溶酶体膜上的调节剂复合物的成分。

与对照组相比，在tmem55b敲除的细胞中，氨基酸诱导的mTORC1底物S6K和4E-BP磷酸化水平减弱。

我们发现TMEM55B的敲除也会引起转录因子TFEB转位到细胞核（溶酶体应激）。

此外，在tmem55b耗尽的细胞中，V-atp酶的V1结构域亚复合物到脂筏上的募集被取消。

综上所述，我们的研究结果表明，TMEM55B有助于溶酶体膜脂筏中VATPase复合物的组装，并参与了随后mTORC1的激活。

原文摘要：

 Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) responds to  growth factors and nutrient availability. 

Amino acids induce the recruitment of  mTORC1 to the lysosomal membrane and its consequent activation, but the molecular mechanism of such activation has remained unclear. 

We have now examined the  role of TMEM55B, a lysosomal protein of unknown molecular function, in this process on the basis of the results of proteomics and immunofluorescence analyses  showing that TMEM55B interacts with many proteins that participate in mTORC1  activation including components of the vacuolar-type proton ATPase (V-ATPase)  and Ragulator complexes at the lysosomal membrane. 

The amino acid–induced  phosphorylation of the mTORC1 substrates S6K and 4E-BP was attenuated in  TMEM55B-depleted cells compared with control cells. 

Depletion of TMEM55B  was also found to evoke lysosomal stress as showed by translocation of the transcription factor TFEB to the nucleus. 

Furthermore, recruitment of the V1 domain subcomplex of V-ATPase to lipid rafts was abrogated in TMEM55B-depleted cells.  

Collectively, our results suggest that TMEM55B contributes to assembly of the VATPase complex in lipid rafts of the lysosomal membrane and to subsequent activation of mTORC1.

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参考文献：https://pubmed.ncbi.nlm./29644770/

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