Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Biological Transport / drug effects
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cell Membrane / ultrastructure
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Endoplasmic Reticulum / drug effects*
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Endoplasmic Reticulum / metabolism
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Endoplasmic Reticulum / ultrastructure
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Exocytosis / drug effects*
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Golgi Apparatus / drug effects*
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Golgi Apparatus / metabolism
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Golgi Apparatus / ultrastructure
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HeLa Cells
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Heterocyclic Compounds, 4 or More Rings / chemistry
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Heterocyclic Compounds, 4 or More Rings / pharmacology*
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Humans
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Microscopy, Electron, Transmission
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Microscopy, Fluorescence
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Molecular Structure
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Nocodazole / pharmacology
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Organic Chemicals / chemistry
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Organic Chemicals / pharmacology*
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Small Molecule Libraries
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Tubulin Modulators / pharmacology
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism
Substances
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G protein, vesicular stomatitis virus
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Heterocyclic Compounds, 4 or More Rings
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Membrane Glycoproteins
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Organic Chemicals
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Small Molecule Libraries
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Tubulin Modulators
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Viral Envelope Proteins
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dispergo
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Green Fluorescent Proteins
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Nocodazole