Cargando…
Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8
The molecular details of the biogenesis of double-membraned autophagosomes are poorly understood. We identify the Saccharomyces cerevisiae AAA–adenosine triphosphatase Cdc48 and its substrate-recruiting cofactor Shp1/Ubx1 as novel components needed for autophagosome biogenesis. In mammals, the Cdc48...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101598/ https://www.ncbi.nlm.nih.gov/pubmed/20855502 http://dx.doi.org/10.1083/jcb.201002075 |
_version_ | 1782204284954214400 |
---|---|
author | Krick, Roswitha Bremer, Sebastian Welter, Evelyn Schlotterhose, Petra Muehe, Yvonne Eskelinen, Eeva-Liisa Thumm, Michael |
author_facet | Krick, Roswitha Bremer, Sebastian Welter, Evelyn Schlotterhose, Petra Muehe, Yvonne Eskelinen, Eeva-Liisa Thumm, Michael |
author_sort | Krick, Roswitha |
collection | PubMed |
description | The molecular details of the biogenesis of double-membraned autophagosomes are poorly understood. We identify the Saccharomyces cerevisiae AAA–adenosine triphosphatase Cdc48 and its substrate-recruiting cofactor Shp1/Ubx1 as novel components needed for autophagosome biogenesis. In mammals, the Cdc48 homologue p97/VCP and the Shp1 homologue p47 mediate Golgi reassembly by extracting an unknown monoubiquitinated fusion regulator from a complex. We find no requirement of ubiquitination or the proteasome system for autophagosome biogenesis but detect interaction of Shp1 with the ubiquitin-fold autophagy protein Atg8. Atg8 coupled to phosphatidylethanolamine (PE) is crucial for autophagosome elongation and, in vitro, mediates tethering and hemifusion. Interaction with Shp1 requires an FK motif within the N-terminal non–ubiquitin-like Atg8 domain. Based on our data, we speculate that autophagosome formation, in contrast to Golgi reassembly, requires a complex in which Atg8 functionally substitutes ubiquitin. This, for the first time, would give a rationale for use of the ubiquitin-like Atg8 during macroautophagy and would explain why Atg8-PE delipidation is necessary for efficient macroautophagy. |
format | Text |
id | pubmed-3101598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31015982011-06-06 Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 Krick, Roswitha Bremer, Sebastian Welter, Evelyn Schlotterhose, Petra Muehe, Yvonne Eskelinen, Eeva-Liisa Thumm, Michael J Cell Biol Research Articles The molecular details of the biogenesis of double-membraned autophagosomes are poorly understood. We identify the Saccharomyces cerevisiae AAA–adenosine triphosphatase Cdc48 and its substrate-recruiting cofactor Shp1/Ubx1 as novel components needed for autophagosome biogenesis. In mammals, the Cdc48 homologue p97/VCP and the Shp1 homologue p47 mediate Golgi reassembly by extracting an unknown monoubiquitinated fusion regulator from a complex. We find no requirement of ubiquitination or the proteasome system for autophagosome biogenesis but detect interaction of Shp1 with the ubiquitin-fold autophagy protein Atg8. Atg8 coupled to phosphatidylethanolamine (PE) is crucial for autophagosome elongation and, in vitro, mediates tethering and hemifusion. Interaction with Shp1 requires an FK motif within the N-terminal non–ubiquitin-like Atg8 domain. Based on our data, we speculate that autophagosome formation, in contrast to Golgi reassembly, requires a complex in which Atg8 functionally substitutes ubiquitin. This, for the first time, would give a rationale for use of the ubiquitin-like Atg8 during macroautophagy and would explain why Atg8-PE delipidation is necessary for efficient macroautophagy. The Rockefeller University Press 2010-09-20 /pmc/articles/PMC3101598/ /pubmed/20855502 http://dx.doi.org/10.1083/jcb.201002075 Text en © 2010 Krick et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Krick, Roswitha Bremer, Sebastian Welter, Evelyn Schlotterhose, Petra Muehe, Yvonne Eskelinen, Eeva-Liisa Thumm, Michael Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 |
title | Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 |
title_full | Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 |
title_fullStr | Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 |
title_full_unstemmed | Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 |
title_short | Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8 |
title_sort | cdc48/p97 and shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like atg8 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101598/ https://www.ncbi.nlm.nih.gov/pubmed/20855502 http://dx.doi.org/10.1083/jcb.201002075 |
work_keys_str_mv | AT krickroswitha cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 AT bremersebastian cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 AT welterevelyn cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 AT schlotterhosepetra cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 AT mueheyvonne cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 AT eskelineneevaliisa cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 AT thummmichael cdc48p97andshp1p47regulateautophagosomebiogenesisinconcertwithubiquitinlikeatg8 |