دورية أكاديمية
Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation.
| العنوان: | Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation. |
|---|---|
| المؤلفون: | Shinoda S; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan., Sakai Y; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan., Matsui T; Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan., Uematsu M; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan., Koyama-Honda I; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan., Sakamaki JI; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan., Yamamoto H; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan., Mizushima N; Department of Biochemistry and Molecular Biology, Graduated School of Medicine, The University of Tokyo, Tokyo, Japan. |
| المصدر: | ELife [Elife] 2024 Jun 04; Vol. 12. Date of Electronic Publication: 2024 Jun 04. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
| مواضيع طبية MeSH: | Qa-SNARE Proteins*/metabolism , Qa-SNARE Proteins*/genetics , Autophagosomes*/metabolism , Phosphatidylinositol Phosphates*/metabolism, Humans ; Molecular Dynamics Simulation ; Autophagy/physiology |
| مستخلص: | During macroautophagy, cytoplasmic constituents are engulfed by autophagosomes. Lysosomes fuse with closed autophagosomes but not with unclosed intermediate structures. This is achieved in part by the late recruitment of the autophagosomal SNARE syntaxin 17 (STX17) to mature autophagosomes. However, how STX17 recognizes autophagosome maturation is not known. Here, we show that this temporally regulated recruitment of STX17 depends on the positively charged C-terminal region of STX17. Consistent with this finding, mature autophagosomes are more negatively charged compared with unclosed intermediate structures. This electrostatic maturation of autophagosomes is likely driven by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane. Accordingly, dephosphorylation of autophagosomal PI4P prevents the association of STX17 to autophagosomes. Furthermore, molecular dynamics simulations support PI4P-dependent membrane insertion of the transmembrane helices of STX17. Based on these findings, we propose a model in which STX17 recruitment to mature autophagosomes is temporally regulated by a PI4P-driven change in the surface charge of autophagosomes. Competing Interests: SS, YS, TM, MU, IK, JS, HY No competing interests declared, NM Reviewing editor, eLife (© 2023, Shinoda et al.) |
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| معلومات مُعتمدة: | 22H04919 Japan Society for the Promotion of Science; 21H05256 Japan Society for the Promotion of Science; 23K05715 Japan Society for the Promotion of Science; 17J02747 Japan Society for the Promotion of Science; JPMJER1702 Exploratory Research for Advanced Technology |
| فهرسة مساهمة: | Keywords: SNARE; autophagosome; autophagy; cell biology; human; membrane charge; mouse; phosphatidylinositol 4-phosphate; syntaxin 17 |
| المشرفين على المادة: | 0 (Qa-SNARE Proteins) 0 (Phosphatidylinositol Phosphates) 0 (phosphatidylinositol 4-phosphate) 0 (STX17 protein, human) |
| تواريخ الأحداث: | Date Created: 20240604 Date Completed: 20240604 Latest Revision: 20240607 |
| رمز التحديث: | 20240607 |
| مُعرف محوري في PubMed: | PMC11152571 |
| DOI: | 10.7554/eLife.92189 |
| PMID: | 38831696 |
| قاعدة البيانات: | MEDLINE |
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