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Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments
At the Golgi complex, the biosynthetic sorting center of the cell, the Arf GTPases are responsible for coordinating vesicle formation. The Arf-GEFs activate Arf GTPases and are therefore the key molecular decision-makers for trafficking from the Golgi. In Saccharomyces cerevisiae, three conserved Ar...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706993/ https://www.ncbi.nlm.nih.gov/pubmed/28978742 http://dx.doi.org/10.1091/mbc.E17-06-0370 |
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author | Gustafson, Margaret A. Fromme, J. Christopher |
author_facet | Gustafson, Margaret A. Fromme, J. Christopher |
author_sort | Gustafson, Margaret A. |
collection | PubMed |
description | At the Golgi complex, the biosynthetic sorting center of the cell, the Arf GTPases are responsible for coordinating vesicle formation. The Arf-GEFs activate Arf GTPases and are therefore the key molecular decision-makers for trafficking from the Golgi. In Saccharomyces cerevisiae, three conserved Arf-GEFs function at the Golgi: Sec7, Gea1, and Gea2. Our group has described the regulation of Sec7, the trans-Golgi Arf-GEF, through autoinhibition, positive feedback, dimerization, and interactions with a suite of small GTPases. However, we lack a clear understanding of the regulation of the early Golgi Arf-GEFs Gea1 and Gea2. Here we demonstrate that Gea1 and Gea2 prefer neutral over anionic membrane surfaces in vitro, consistent with their localization to the early Golgi. We illustrate a requirement for a critical mass of either Gea1 or Gea2 for cell growth under stress conditions. We show that the C-terminal domains of Gea1 and Gea2 toggle roles in the cytosol and at the membrane surface, preventing membrane binding in the absence of a recruiting interaction but promoting maximum catalytic activity once recruited. We also identify the small GTPase Ypt1 as a recruiter for Gea1 and Gea2. Our findings illuminate core regulatory mechanisms unique to the early Golgi Arf-GEFs. |
format | Online Article Text |
id | pubmed-5706993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-57069932018-02-16 Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments Gustafson, Margaret A. Fromme, J. Christopher Mol Biol Cell Articles At the Golgi complex, the biosynthetic sorting center of the cell, the Arf GTPases are responsible for coordinating vesicle formation. The Arf-GEFs activate Arf GTPases and are therefore the key molecular decision-makers for trafficking from the Golgi. In Saccharomyces cerevisiae, three conserved Arf-GEFs function at the Golgi: Sec7, Gea1, and Gea2. Our group has described the regulation of Sec7, the trans-Golgi Arf-GEF, through autoinhibition, positive feedback, dimerization, and interactions with a suite of small GTPases. However, we lack a clear understanding of the regulation of the early Golgi Arf-GEFs Gea1 and Gea2. Here we demonstrate that Gea1 and Gea2 prefer neutral over anionic membrane surfaces in vitro, consistent with their localization to the early Golgi. We illustrate a requirement for a critical mass of either Gea1 or Gea2 for cell growth under stress conditions. We show that the C-terminal domains of Gea1 and Gea2 toggle roles in the cytosol and at the membrane surface, preventing membrane binding in the absence of a recruiting interaction but promoting maximum catalytic activity once recruited. We also identify the small GTPase Ypt1 as a recruiter for Gea1 and Gea2. Our findings illuminate core regulatory mechanisms unique to the early Golgi Arf-GEFs. The American Society for Cell Biology 2017-12-01 /pmc/articles/PMC5706993/ /pubmed/28978742 http://dx.doi.org/10.1091/mbc.E17-06-0370 Text en © 2017 Gustafson and Fromme. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Gustafson, Margaret A. Fromme, J. Christopher Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments |
title | Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments |
title_full | Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments |
title_fullStr | Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments |
title_full_unstemmed | Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments |
title_short | Regulation of Arf activation occurs via distinct mechanisms at early and late Golgi compartments |
title_sort | regulation of arf activation occurs via distinct mechanisms at early and late golgi compartments |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706993/ https://www.ncbi.nlm.nih.gov/pubmed/28978742 http://dx.doi.org/10.1091/mbc.E17-06-0370 |
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