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Dynamics and function of PtdIns(3)P in autophagy.
| Title: | Dynamics and function of PtdIns(3)P in autophagy. |
| Authors: | Obara, Keisuke Browse this author | | Ohsumi, Yoshinori Browse this author |
| Keywords: | autophagy | | isolation membrane | | autophagosome | | PtdIns(3)P | | Atg18 | | phosphoinositide | | PtdIns 3-kinase | | Vps34 |
| Issue Date: | 1-Oct-2008 |
| Publisher: | Landes Bioscience |
| Journal Title: | Autophagy |
| Volume: | 4 |
| Issue: | 7 |
| Start Page: | 952 |
| End Page: | 954 |
| PMID: | 18769109 |
| Abstract: | Phosphorylation of phosphatidylinositol (PtdIns) by PtdIns 3-kinase is essential for autophagy. However, the distribution and function of the enzymatic product, PtdIns 3-phosphate (PtdIns(3)P), has been unknown. We monitored PtdIns(3)P distribution during autophagy by live imaging, biochemistry, and electron microscopy, and found that PtdIns(3)P is massively delivered into the vacuole via autophagy. PtdIns(3)P is highly enriched as a membrane component of the elongating isolation membranes and autophagosome membranes rather than as an enclosed cargo, implying direct involvement of PtdIns(3)P in autophagosome formation. This observation also provides important basic information on the nature of the autophagosome membrane, which is still poorly understood. Notably, PtdIns(3)P is highly enriched on the inner (concave) surfaces of the isolation membrane and autophagosome compared to the outer surfaces. PtdIns(3)P is also enriched on ambiguous structures juxtaposed to the elongating tips of isolation membranes. We also investigated the function of PtdIns(3)P in autophagy, and show that PtdIns(3)P recruits the Atg18-Atg2 complex to autophagic membranes through an Atg18-PtdIns(3)P interaction. Interestingly, PtdIns(3)P is required only for the association of the Atg18-Atg2 complex to autophagic membranes but not for any subsequent functional activity of the Atg18-Atg2 complex, suggesting that PtdIns(3)P does not act allosterically on Atg18. Based on these results we discuss the function of PtdIns(3)P in autophagy. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/45477 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 小原 圭介
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