دورية أكاديمية
أعرض في EDS

PtdIns4P is required for the autophagosomal recruitment of STX17 (syntaxin 17) to promote lysosomal fusion.

التفاصيل البيبلوغرافية
العنوان: PtdIns4P is required for the autophagosomal recruitment of STX17 (syntaxin 17) to promote lysosomal fusion.
المؤلفون: Laczkó-Dobos H; Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Bhattacharjee A; Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Maddali AK; Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary.; Doctoral School of Biology, University of Szeged, Szeged, Hungary., Kincses A; Institute of Biophysics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Abuammar H; Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary.; Doctoral School of Biology, University of Szeged, Szeged, Hungary., Sebők-Nagy K; Institute of Biophysics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Páli T; Institute of Biophysics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Dér A; Institute of Biophysics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Hegedűs T; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.; HUN-REN Biophysical Virology Research Group, Budapest, Hungary., Csordás G; Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary., Juhász G; Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary.; Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
المصدر: Autophagy [Autophagy] 2024 Jul; Vol. 20 (7), pp. 1639-1650. Date of Electronic Publication: 2024 Mar 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101265188 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8635 (Electronic) Linking ISSN: 15548627 NLM ISO Abbreviation: Autophagy Subsets: MEDLINE
أسماء مطبوعة: Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Georgetown, TX : Landes Bioscience, 2005-
مواضيع طبية MeSH: Lysosomes*/metabolism , Autophagosomes*/metabolism , Membrane Fusion*/drug effects , Qa-SNARE Proteins*/metabolism , Phosphatidylinositol Phosphates*/metabolism, Humans ; Autophagy/physiology ; Autophagy/drug effects ; Liposomes/metabolism ; Molecular Dynamics Simulation ; HeLa Cells
مستخلص: The autophagosomal SNARE STX17 (syntaxin 17) promotes lysosomal fusion and degradation, but its autophagosomal recruitment is incompletely understood. Notably, PtdIns4P is generated on autophagosomes and promotes fusion through an unknown mechanism. Here we show that soluble recombinant STX17 is spontaneously recruited to negatively charged liposomes and adding PtdIns4P to liposomes containing neutral lipids is sufficient for its recruitment. Consistently, STX17 colocalizes with PtdIns4P-positive autophagosomes in cells, and specific inhibition of PtdIns4P synthesis on autophagosomes prevents its loading. Molecular dynamics simulations indicate that C-terminal positively charged amino acids establish contact with membrane bilayers containing negatively charged PtdIns4P. Accordingly, Ala substitution of Lys and Arg residues in the C terminus of STX17 abolishes membrane binding and impairs its autophagosomal recruitment. Finally, only wild type but not Ala substituted STX17 expression rescues the autophagosome-lysosome fusion defect of STX17 loss-of-function cells. We thus identify a key step of autophagosome maturation that promotes lysosomal fusion. Abbreviations: Cardiolipin: 1',3'-bis[1-palmitoyl-2-oleoyl-sn-glycero-3-phospho]-glycerol; DMSO: dimethyl sulfoxide; GST: glutathione S-transferase; GUV: giant unilamellar vesicles; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PA: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate; PC/POPC: 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine; PG: 1-palmitoyl-2-linoleoyl-sn-glycero-3-phospho-(1'-rac-glycerol); PI: L-α-phosphatidylinositol; PI4K2A: phosphatidylinositol 4-kinase type 2 alpha; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; POPE/PE: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine; PS: 1-stearoyl-2-linoleoyl-sn-glycero-3-phospho-L-serine; PtdIns(3,5)P 2 : 1,2-dioleoyl-sn-glycero-3-phospho-(1"-myo-inositol-3',5'-bisphosphate); PtdIns3P: 1,2- dioleoyl-sn-glycero-3-phospho-(1'-myo-inositol-3'-phosphate); PtdIns4P: 1,2-dioleoyl-sn-glycero-3-phospho-(1"-myo-inositol-4'-phosphate); SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; STX17: syntaxin 17.
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فهرسة مساهمة: Keywords: Autophagosome; PI4K2A; autophagy; coincidence detection; electrostatic interaction; phosphoinositide
المشرفين على المادة: 0 (Qa-SNARE Proteins)
0 (phosphatidylinositol 4-phosphate)
0 (Phosphatidylinositol Phosphates)
0 (STX17 protein, human)
0 (Liposomes)
تواريخ الأحداث: Date Created: 20240227 Date Completed: 20240626 Latest Revision: 20240629
رمز التحديث: 20240629
مُعرف محوري في PubMed: PMC11210929
DOI: 10.1080/15548627.2024.2322493
PMID: 38411137
قاعدة البيانات: MEDLINE
الوصف
تدمد:1554-8635
DOI:10.1080/15548627.2024.2322493