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The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway

Autophagy and the Cvt pathway are examples of nonclassical vesicular transport from the cytoplasm to the vacuole via double-membrane vesicles. Apg8/Aut7, which plays an important role in the formation of such vesicles, tends to bind to membranes in spite of its hydrophilic nature. We show here that...

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Autores principales: Kirisako, Takayoshi, Ichimura, Yoshinobu, Okada, Hisashi, Kabeya, Yukiko, Mizushima, Noboru, Yoshimori, Tamotsu, Ohsumi, Mariko, Takao, Toshifumi, Noda, Takeshi, Ohsumi, Yoshinori
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192639/
https://www.ncbi.nlm.nih.gov/pubmed/11038174
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author Kirisako, Takayoshi
Ichimura, Yoshinobu
Okada, Hisashi
Kabeya, Yukiko
Mizushima, Noboru
Yoshimori, Tamotsu
Ohsumi, Mariko
Takao, Toshifumi
Noda, Takeshi
Ohsumi, Yoshinori
author_facet Kirisako, Takayoshi
Ichimura, Yoshinobu
Okada, Hisashi
Kabeya, Yukiko
Mizushima, Noboru
Yoshimori, Tamotsu
Ohsumi, Mariko
Takao, Toshifumi
Noda, Takeshi
Ohsumi, Yoshinori
author_sort Kirisako, Takayoshi
collection PubMed
description Autophagy and the Cvt pathway are examples of nonclassical vesicular transport from the cytoplasm to the vacuole via double-membrane vesicles. Apg8/Aut7, which plays an important role in the formation of such vesicles, tends to bind to membranes in spite of its hydrophilic nature. We show here that the nature of the association of Apg8 with membranes changes depending on a series of modifications of the protein itself. First, the carboxy-terminal Arg residue of newly synthesized Apg8 is removed by Apg4/Aut2, a novel cysteine protease, and a Gly residue becomes the carboxy-terminal residue of the protein that is now designated Apg8FG. Subsequently, Apg8FG forms a conjugate with an unidentified molecule “X” and thereby binds tightly to membranes. This modification requires the carboxy-terminal Gly residue of Apg8FG and Apg7, a ubiquitin E1-like enzyme. Finally, the adduct Apg8FG-X is reversed to soluble or loosely membrane-bound Apg8FG by cleavage by Apg4. The mode of action of Apg4, which cleaves both newly synthesized Apg8 and modified Apg8FG, resembles that of deubiquitinating enzymes. A reaction similar to ubiquitination is probably involved in the second modification. The reversible modification of Apg8 appears to be coupled to the membrane dynamics of autophagy and the Cvt pathway.
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spelling pubmed-21926392008-05-01 The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway Kirisako, Takayoshi Ichimura, Yoshinobu Okada, Hisashi Kabeya, Yukiko Mizushima, Noboru Yoshimori, Tamotsu Ohsumi, Mariko Takao, Toshifumi Noda, Takeshi Ohsumi, Yoshinori J Cell Biol Original Article Autophagy and the Cvt pathway are examples of nonclassical vesicular transport from the cytoplasm to the vacuole via double-membrane vesicles. Apg8/Aut7, which plays an important role in the formation of such vesicles, tends to bind to membranes in spite of its hydrophilic nature. We show here that the nature of the association of Apg8 with membranes changes depending on a series of modifications of the protein itself. First, the carboxy-terminal Arg residue of newly synthesized Apg8 is removed by Apg4/Aut2, a novel cysteine protease, and a Gly residue becomes the carboxy-terminal residue of the protein that is now designated Apg8FG. Subsequently, Apg8FG forms a conjugate with an unidentified molecule “X” and thereby binds tightly to membranes. This modification requires the carboxy-terminal Gly residue of Apg8FG and Apg7, a ubiquitin E1-like enzyme. Finally, the adduct Apg8FG-X is reversed to soluble or loosely membrane-bound Apg8FG by cleavage by Apg4. The mode of action of Apg4, which cleaves both newly synthesized Apg8 and modified Apg8FG, resembles that of deubiquitinating enzymes. A reaction similar to ubiquitination is probably involved in the second modification. The reversible modification of Apg8 appears to be coupled to the membrane dynamics of autophagy and the Cvt pathway. The Rockefeller University Press 2000-10-16 /pmc/articles/PMC2192639/ /pubmed/11038174 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Kirisako, Takayoshi
Ichimura, Yoshinobu
Okada, Hisashi
Kabeya, Yukiko
Mizushima, Noboru
Yoshimori, Tamotsu
Ohsumi, Mariko
Takao, Toshifumi
Noda, Takeshi
Ohsumi, Yoshinori
The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway
title The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway
title_full The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway
title_fullStr The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway
title_full_unstemmed The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway
title_short The Reversible Modification Regulates the Membrane-Binding State of Apg8/Aut7 Essential for Autophagy and the Cytoplasm to Vacuole Targeting Pathway
title_sort reversible modification regulates the membrane-binding state of apg8/aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192639/
https://www.ncbi.nlm.nih.gov/pubmed/11038174
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