The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes
Abstract
Nuclear pore complexes (NPCs) regulate all cargo traffic across the nuclear envelope. The transport conduit of NPCs is highly enriched in disordered phenylalanine/glycine-rich nucleoporins (FG-Nups), which form a permeability barrier of still elusive and highly debated molecular structure. Here we present a microfluidic device that triggered liquid-to-liquid phase separation of FG-Nups, which yielded droplets that showed typical properties of a liquid state. On the microfluidic chip, droplets were perfused with different transport-competent or -incompetent cargo complexes, and then the permeability barrier properties of the droplets were optically interrogated. We show that the liquid state mimics permeability barrier properties of the physiological nuclear transport pathway in intact NPCs in cells: that is, inert cargoes ranging from small proteins to large capsids were excluded from liquid FG-Nup droplets, but functional import complexes underwent facilitated import into droplets. Collectively, these data provide an experimental model of how NPCs can facilitate fast passage of cargoes across an order of magnitude in cargo size.
- Authors:
-
[1];
[1];
[1];
[2];
[1]
- Biocentre, Johannes Gutenberg-University Mainz, Mainz, Germany, Institute of Molecular Biology, Mainz, Germany, Structural and Computational Biology Unit and Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany
- Center for Integrated Nanotechnologies, Sandia National Laboratories, Albuquerque, NM
- Publication Date:
- Research Org.:
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE National Nuclear Security Administration (NNSA)
- OSTI Identifier:
- 1574083
- Alternate Identifier(s):
- OSTI ID: 1595029
- Report Number(s):
- SAND-2019-14345J
Journal ID: ISSN 0021-9525; e201907157
- Grant/Contract Number:
- AC04-94AL85000; NA-0003525
- Resource Type:
- Published Article
- Journal Name:
- Journal of Cell Biology
- Additional Journal Information:
- Journal Name: Journal of Cell Biology Journal Volume: 219 Journal Issue: 1; Journal ID: ISSN 0021-9525
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; FG-Nups; phase separation; nuclear transport; microfluids
Citation Formats
Celetti, Giorgia, Paci, Giulia, Caria, Joana, VanDelinder, Virginia, Bachand, George, and Lemke, Edward A. The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes. United States: N. p., 2019.
Web. doi:10.1083/jcb.201907157.
Celetti, Giorgia, Paci, Giulia, Caria, Joana, VanDelinder, Virginia, Bachand, George, & Lemke, Edward A. The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes. United States. https://doi.org/10.1083/jcb.201907157
Celetti, Giorgia, Paci, Giulia, Caria, Joana, VanDelinder, Virginia, Bachand, George, and Lemke, Edward A. Wed .
"The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes". United States. https://doi.org/10.1083/jcb.201907157.
@article{osti_1574083,
title = {The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes},
author = {Celetti, Giorgia and Paci, Giulia and Caria, Joana and VanDelinder, Virginia and Bachand, George and Lemke, Edward A.},
abstractNote = {Nuclear pore complexes (NPCs) regulate all cargo traffic across the nuclear envelope. The transport conduit of NPCs is highly enriched in disordered phenylalanine/glycine-rich nucleoporins (FG-Nups), which form a permeability barrier of still elusive and highly debated molecular structure. Here we present a microfluidic device that triggered liquid-to-liquid phase separation of FG-Nups, which yielded droplets that showed typical properties of a liquid state. On the microfluidic chip, droplets were perfused with different transport-competent or -incompetent cargo complexes, and then the permeability barrier properties of the droplets were optically interrogated. We show that the liquid state mimics permeability barrier properties of the physiological nuclear transport pathway in intact NPCs in cells: that is, inert cargoes ranging from small proteins to large capsids were excluded from liquid FG-Nup droplets, but functional import complexes underwent facilitated import into droplets. Collectively, these data provide an experimental model of how NPCs can facilitate fast passage of cargoes across an order of magnitude in cargo size.},
doi = {10.1083/jcb.201907157},
journal = {Journal of Cell Biology},
number = 1,
volume = 219,
place = {United States},
year = {2019},
month = {11}
}
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https://doi.org/10.1083/jcb.201907157
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