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Research Paper
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 and Eiki Kominami
volume 2 | issue 4
October/November/December 2006Pages: 264 - 271
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Although a conjugation of overexpressed GABARAP to phospholipid has been reported to be activated during starvation-induced autophagy, it is unclear whether endogenous GABARAP-conjugation is also activated under starvation conditions. We observed that little GABARAP-phospholipid conjugate (GABARAP-PL) accumulated in mouse liver and kidney under starvation conditions, while 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, the accumulation of GABARAP-PL in the presence of lysosomal protease inhibitors is independent of starvation-induced autophagy, whereas the accumulation of LC3-II in their presence is significantly activated during starvation-induced autophagy. Interestingly, we observed that the lysosomal turnover of GABARAP-PL is activated during the differentiation of C2C12 cells to myotubes. Under these conditions, S6 ribosomal protein is still phosphorylated, suggesting that mTor kinase-signaling pathway is active during the differentiation of C2C12 cells to myotubes, different from the case during starvation-induced autophagy. These results indicated that the lysosomal turnover of GABARAP-PL is activated during the differentiation of C2C12 cells to myotubes without inactivation of mTor kinase-signaling pathway, while little is activated during starvation-induced autophagy.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.