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

Yutaka Hashimoto, Michiko Shirane, Keiichi I. Nakayama

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

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 V-ATPase complex in lipid rafts of the lysosomal membrane and to subsequent activation of mTORC1.

本文言語英語
ページ(範囲)418-434
ページ数17
ジャーナルGenes to Cells
23
6
DOI
出版ステータス出版済み - 6 2018
外部発表はい

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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