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The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export

The mammalian endoplasmic reticulum (ER) is an organelle that maintains a complex, compartmentalized organization of interconnected cisternae and tubules while supporting a continuous flow of newly synthesized proteins and lipids to the Golgi apparatus. Using a phenotypic screen, we identify a small...

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Detalles Bibliográficos
Autores principales: Lu, Lei, Hannoush, Rami N., Goess, Brian C., Varadarajan, Shankar, Shair, Matthew D., Kirchhausen, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608490/
https://www.ncbi.nlm.nih.gov/pubmed/23389632
http://dx.doi.org/10.1091/mbc.E12-08-0575
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author Lu, Lei
Hannoush, Rami N.
Goess, Brian C.
Varadarajan, Shankar
Shair, Matthew D.
Kirchhausen, Tom
author_facet Lu, Lei
Hannoush, Rami N.
Goess, Brian C.
Varadarajan, Shankar
Shair, Matthew D.
Kirchhausen, Tom
author_sort Lu, Lei
collection PubMed
description The mammalian endoplasmic reticulum (ER) is an organelle that maintains a complex, compartmentalized organization of interconnected cisternae and tubules while supporting a continuous flow of newly synthesized proteins and lipids to the Golgi apparatus. Using a phenotypic screen, we identify a small molecule, dispergo, that induces reversible loss of the ER cisternae and extensive ER tubulation, including formation of ER patches comprising densely packed tubules. Dispergo also prevents export from the ER to the Golgi apparatus, and this traffic block results in breakdown of the Golgi apparatus, primarily due to maintenance of the constitutive retrograde transport of its components to the ER. The effects of dispergo are reversible, since its removal allows recovery of the ER cisternae at the expense of the densely packed tubular ER patches. This recovery occurs together with reactivation of ER-to-Golgi traffic and regeneration of a functional Golgi with correct morphology. Because dispergo is the first small molecule that reversibly tubulates the ER and inhibits its export function, it will be useful in studying these complex processes.
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spelling pubmed-36084902013-06-16 The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export Lu, Lei Hannoush, Rami N. Goess, Brian C. Varadarajan, Shankar Shair, Matthew D. Kirchhausen, Tom Mol Biol Cell Articles The mammalian endoplasmic reticulum (ER) is an organelle that maintains a complex, compartmentalized organization of interconnected cisternae and tubules while supporting a continuous flow of newly synthesized proteins and lipids to the Golgi apparatus. Using a phenotypic screen, we identify a small molecule, dispergo, that induces reversible loss of the ER cisternae and extensive ER tubulation, including formation of ER patches comprising densely packed tubules. Dispergo also prevents export from the ER to the Golgi apparatus, and this traffic block results in breakdown of the Golgi apparatus, primarily due to maintenance of the constitutive retrograde transport of its components to the ER. The effects of dispergo are reversible, since its removal allows recovery of the ER cisternae at the expense of the densely packed tubular ER patches. This recovery occurs together with reactivation of ER-to-Golgi traffic and regeneration of a functional Golgi with correct morphology. Because dispergo is the first small molecule that reversibly tubulates the ER and inhibits its export function, it will be useful in studying these complex processes. The American Society for Cell Biology 2013-04-01 /pmc/articles/PMC3608490/ /pubmed/23389632 http://dx.doi.org/10.1091/mbc.E12-08-0575 Text en © 2013 Lu et al. 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 of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Lu, Lei
Hannoush, Rami N.
Goess, Brian C.
Varadarajan, Shankar
Shair, Matthew D.
Kirchhausen, Tom
The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
title The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
title_full The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
title_fullStr The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
title_full_unstemmed The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
title_short The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
title_sort small molecule dispergo tubulates the endoplasmic reticulum and inhibits export
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608490/
https://www.ncbi.nlm.nih.gov/pubmed/23389632
http://dx.doi.org/10.1091/mbc.E12-08-0575
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