University of Leicester
Browse
Mol. Biol. Cell-2013-Lu-1020-9.pdf (2.29 MB)

The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export

Download (2.29 MB)
journal contribution
posted on 2016-02-25, 12:30 authored by L. Lu, R. N. Hannoush, B. C. Goess, Shankar Varadarajan, M. D. Shair, T. Kirchhausen
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.

Funding

R.H. was a recipient of postdoctoral fellowships from the Canadian Institutes of Health Research and National Sciences and Engineering Research Council of Canada. B.G. was a recipient of a doctoral fellowship from the U.S. Department of Defense (National Defense Science and Engineering Graduate Fellowship). This work was supported in part by National Institutes of Health Grant GM-075252 (to T.K.) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility, Boston, MA), as well as P01 GM62556 (to T.K. and M.S.) and SBS SUG M58080013 (to L.L.).

History

Citation

Molecular Biology of the Cell April 1, 2013 vol. 24 no. 7 1020-1029

Version

  • VoR (Version of Record)

Published in

Molecular Biology of the Cell April 1

Publisher

American Society for Cell Biology

issn

1059-1524

eissn

1939-4586

Acceptance date

2013-01-30

Copyright date

2013

Available date

2016-02-25

Publisher version

http://www.molbiolcell.org/content/24/7/1020

Notes

Supplemental Material can be found at: http://www.molbiolcell.org/content/suppl/2013/02/04/mbc.E12-08-0575.DC1.html

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    Keywords

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC