The Atg18-Atg2 Complex Is Recruited to Autophagic Membranes via Phosphatidylinositol 3-Phosphate and Exerts an Essential Function

• Obara, Keisuke

• Sekito, Takayuki

• Niimi, Kaori

• Ohsumi, Yoshinori

抄録

Atg18 is essential for both autophagy and the regulation of vacuolar morphology. The latter process is mediated by PtdIns(3,5)P2 binding, which is dispensable for autophagy. Atg18 also binds to PtdIns(3)P in vitro. Here, we investigate the relationship between PtdIns(3)P-binding of Atg18 and autophagy. Using an Atg18 variant, Atg18(FTTG), which is unable to bind phosphoinositides, we found that PtdIns(3)P-binding of Atg18 is essential for full activity in both selective and non-selective autophagy. Atg18(FTTG) formed a complex with Atg2 in a normal manner, and Atg18-Atg2 complex formation occurred in cells in the absence of PtdIns(3)P, indicating that Atg18-Atg2 complex formation is independent of PtdIns(3)P-binding of Atg18. Atg18 localized to endosomes, the vacuolar membrane, and autophagic membranes, while Atg18(FTTG) did not localize to these structures. The localization of Atg2 to autophagic membranes was also lost in Atg18(FTTG) cells. These data indicate that PtdIns(3)P-binding of Atg18 is involved in directing the Atg18-Atg2 complex to autophagic membranes. Connection of a 2xFYVE domain, a specific PtdIns(3)P-binding domain, to the C-terminus of Atg18(FTTG) restored the localization of Atg18-Atg2 to autophagic membranes and full autophagic activity, indicating that PtdIns(3)P-binding by Atg18 is dispensable for the function of Atg18-Atg2 complex but is required for its localization. This also suggests that PtdIns(3)P does not act allosterically on Atg18. Taken together, Atg18 forms a complex with Atg2 irrespective of PtdIns(3)P-binding, associates tightly to autophagic membranes by interacting with PtdIns(3)P, and plays an essential role.

収録刊行物

• Journal of Biological Chemistry

  Journal of Biological Chemistry 283 (35), 23972-23980, 2008-08

  American Society of Biochemistry and Molecular Biology

詳細情報

• CRID: 1050282813984970752
• NII論文ID: 120003005572
• NII書誌ID: AA1202441X
• ISSN: 1083351X
• ISSN: 00219258
• HANDLE: 2115/45463
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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