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

Yutaka Hashimoto, Michiko Shirane, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

1 引用 (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.

元の言語英語
ページ(範囲)418-434
ページ数17
ジャーナルGenes to Cells
23
発行部数6
DOI
出版物ステータス出版済み - 6 2018

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Vacuolar Proton-Translocating ATPases
Homeostasis
Protons
Membranes
Lipids
Proteomics
Fluorescent Antibody Technique
Intercellular Signaling Peptides and Proteins
Transcription Factors
Phosphorylation
mechanistic target of rapamycin complex 1
Amino Acids
Food
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

これを引用

TMEM55B contributes to lysosomal homeostasis and amino acid–induced mTORC1 activation. / Hashimoto, Yutaka; Shirane, Michiko; Nakayama, Keiichi I.

:: Genes to Cells, 巻 23, 番号 6, 06.2018, p. 418-434.

研究成果: ジャーナルへの寄稿記事

Hashimoto, Yutaka ; Shirane, Michiko ; Nakayama, Keiichi I. / TMEM55B contributes to lysosomal homeostasis and amino acid–induced mTORC1 activation. :: Genes to Cells. 2018 ; 巻 23, 番号 6. pp. 418-434.
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abstract = "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.",
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