Lysosomal turnover of GABARAP-phospholipid conjugate is activated during differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway

Isei Tanida, Mika Wakabayashi, Takashi Kanematsu, Naoko Minematsu-Ikeguchi, Yu Shin Sou, Masato Hirata, Takashi Ueno, Eiki Kominami

Research output: Contribution to journalArticle

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Abstract

Although conjugation of overexpressed GABARP to phospholipid has been reported during starvation-induced autophagy, it is unclear whether endogenous GABARAP-phospholipid conjugation is also activated under starvation conditions. We observed little accumulation of GABARAP-phospholipid conjugate (GABARAP-PL) in mouse liver and kidney under starvation conditions, whereas endogenous LC3-phospholipid conjugate (LC3-II) accumulated. A small amount of endogenous GABARAP-PL was observed in the heart, independent of starvation. In rapamycin-treated HEK293 cells, there was little accumulation of endogenous GABARAP-PL, even in the presence of lysosomal protease-inhibitors, whereas there was significant accumulation of endogenous LC3-II, together with inactivation of the mTor kinase-signaling pathway. In HeLa and C2C12 cells, GABARAP-PL accumulation in the presence of lysosomal protease inhibitors was independent of starvation-induced autophagy, whereas LC3-II accumulation was significant during starvation-induced autophagy. Interestingly, we observed activation of lysosomal turnover of GABARAP-PL during the differentiation of C2C12 cells to myotubes, along with increased lysosomal turnover of LC3-II. Under these conditions, S6 ribosomal protein was still phosphorylated, suggesting that the mTor kinase-signaling pathway is active during the differentiation of C2C12 cells to myotubes, in contrast to starvation-induced autophagy. These results indicated that lysosomal turnover of GABARAP-PL was activated during the differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway, whereas little lysosomal turnover of GABARAP-PL was activated during starvation-induced autophagy.

Original languageEnglish
Pages (from-to)264-271
Number of pages8
JournalAutophagy
Volume2
Issue number4
DOIs
Publication statusPublished - Jan 1 2006

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Skeletal Muscle Fibers
Cell Differentiation
Phospholipids
Phosphotransferases
Starvation
Autophagy
Protease Inhibitors
Ribosomal Protein S6
HEK293 Cells
Sirolimus
HeLa Cells

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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Lysosomal turnover of GABARAP-phospholipid conjugate is activated during differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway. / Tanida, Isei; Wakabayashi, Mika; Kanematsu, Takashi; Minematsu-Ikeguchi, Naoko; Sou, Yu Shin; Hirata, Masato; Ueno, Takashi; Kominami, Eiki.

In: Autophagy, Vol. 2, No. 4, 01.01.2006, p. 264-271.

Research output: Contribution to journalArticle

Tanida, Isei ; Wakabayashi, Mika ; Kanematsu, Takashi ; Minematsu-Ikeguchi, Naoko ; Sou, Yu Shin ; Hirata, Masato ; Ueno, Takashi ; Kominami, Eiki. / Lysosomal turnover of GABARAP-phospholipid conjugate is activated during differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway. In: Autophagy. 2006 ; Vol. 2, No. 4. pp. 264-271.
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