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The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation
by
Ohsumi, Yoshinori
, Kirisako, Hiromi
, Koizumi, Michiko
, Kotani, Tetsuya
, Nakatogawa, Hitoshi
in
Autophagosomes - chemistry
/ Autophagosomes - metabolism
/ Autophagy
/ Autophagy-Related Proteins - genetics
/ Autophagy-Related Proteins - metabolism
/ Baking yeast
/ Biodegradation
/ Biological Sciences
/ Biosynthesis
/ Cell Biology
/ Domains
/ Endoplasmic reticulum
/ Endoplasmic Reticulum - metabolism
/ Intracellular Membranes - metabolism
/ Lysosomes
/ Membrane proteins
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Membrane vesicles
/ Membranes
/ Molecular biology
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Phagocytosis
/ Phagosomes
/ Phosphatidylinositol 3-phosphate
/ Phosphatidylinositol Phosphates - metabolism
/ Protein Domains
/ Protein expression
/ Proteins
/ Saccharomyces cerevisiae
/ Saccharomyces cerevisiae - cytology
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Tethers
/ Vacuoles
/ Yeast
2018
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The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation
by
Ohsumi, Yoshinori
, Kirisako, Hiromi
, Koizumi, Michiko
, Kotani, Tetsuya
, Nakatogawa, Hitoshi
in
Autophagosomes - chemistry
/ Autophagosomes - metabolism
/ Autophagy
/ Autophagy-Related Proteins - genetics
/ Autophagy-Related Proteins - metabolism
/ Baking yeast
/ Biodegradation
/ Biological Sciences
/ Biosynthesis
/ Cell Biology
/ Domains
/ Endoplasmic reticulum
/ Endoplasmic Reticulum - metabolism
/ Intracellular Membranes - metabolism
/ Lysosomes
/ Membrane proteins
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Membrane vesicles
/ Membranes
/ Molecular biology
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Phagocytosis
/ Phagosomes
/ Phosphatidylinositol 3-phosphate
/ Phosphatidylinositol Phosphates - metabolism
/ Protein Domains
/ Protein expression
/ Proteins
/ Saccharomyces cerevisiae
/ Saccharomyces cerevisiae - cytology
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Tethers
/ Vacuoles
/ Yeast
2018
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The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation
by
Ohsumi, Yoshinori
, Kirisako, Hiromi
, Koizumi, Michiko
, Kotani, Tetsuya
, Nakatogawa, Hitoshi
in
Autophagosomes - chemistry
/ Autophagosomes - metabolism
/ Autophagy
/ Autophagy-Related Proteins - genetics
/ Autophagy-Related Proteins - metabolism
/ Baking yeast
/ Biodegradation
/ Biological Sciences
/ Biosynthesis
/ Cell Biology
/ Domains
/ Endoplasmic reticulum
/ Endoplasmic Reticulum - metabolism
/ Intracellular Membranes - metabolism
/ Lysosomes
/ Membrane proteins
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Membrane vesicles
/ Membranes
/ Molecular biology
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Phagocytosis
/ Phagosomes
/ Phosphatidylinositol 3-phosphate
/ Phosphatidylinositol Phosphates - metabolism
/ Protein Domains
/ Protein expression
/ Proteins
/ Saccharomyces cerevisiae
/ Saccharomyces cerevisiae - cytology
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Tethers
/ Vacuoles
/ Yeast
2018
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The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation
Journal Article
The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation
2018
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Overview
The biogenesis of double-membrane vesicles called autophagosomes, which sequester and transport intracellular material for degradation in lysosomes or vacuoles, is a central event in autophagy. This process requires a unique set of factors called autophagy-related (Atg) proteins. The Atg proteins assemble to organize the preautophagosomal structure (PAS), at which a cup-shaped membrane, the isolation membrane (or phagophore), forms and expands to become the autophagosome. The molecular mechanism of autophagosome biogenesis remains poorly understood. Previous studies have shown that Atg2 forms a complex with the phosphatidylinositol 3-phosphate (PI3P)-binding protein Atg18 and localizes to the PAS to initiate autophagosome biogenesis; however, the molecular function of Atg2 remains unknown. In this study, we show that Atg2 has two membrane-binding domains in the N- and C-terminal regions and acts as a membrane tether during autophagosome formation in the budding yeast Saccharomyces cerevisiae. An amphipathic helix in the C-terminal region binds to membranes and facilitates Atg18 binding to PI3P to target the Atg2-Atg18 complex to the PAS. The N-terminal region of Atg2 is also involved in the membrane binding of this protein but is dispensable for the PAS targeting of the Atg2-Atg18 complex. Our data suggest that this region associates with the endoplasmic reticulum (ER) and is responsible for the formation of the isolation membrane at the PAS. Based on these results, we propose that the Atg2-Atg18 complex tethers the PAS to the ER to initiate membrane expansion during autophagosome formation.
Publisher
National Academy of Sciences
Subject
/ Autophagy-Related Proteins - genetics
/ Autophagy-Related Proteins - metabolism
/ Domains
/ Endoplasmic Reticulum - metabolism
/ Intracellular Membranes - metabolism
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Multiprotein Complexes - chemistry
/ Multiprotein Complexes - metabolism
/ Phosphatidylinositol 3-phosphate
/ Phosphatidylinositol Phosphates - metabolism
/ Proteins
/ Saccharomyces cerevisiae - cytology
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - genetics
/ Saccharomyces cerevisiae Proteins - metabolism
/ Tethers
/ Vacuoles
/ Yeast
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