Nanotechnology Now

Our NanoNews Digest Sponsors





Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > QB3 researchers illuminate operation of molecular gateway to the cell nucleus

The nuclear pore complex (NPC) gates the traffic of all molecules between the cytoplasm and the nucleus of eukaryotic cells. (a) Larger cargos (red) require a transport receptor (green) to pass through the gate. (b) A quantum dot cargo moves through an NPC. Image: Alan Lowe
The nuclear pore complex (NPC) gates the traffic of all molecules between the cytoplasm and the nucleus of eukaryotic cells. (a) Larger cargos (red) require a transport receptor (green) to pass through the gate. (b) A quantum dot cargo moves through an NPC. Image: Alan Lowe

Abstract:
QB3 biophysicists have traced with unprecedented resolution the paths of cargos moving through the nuclear pore complex (NPC), a selective nanoscale aperture that controls access to the cell's nucleus, and answered several key questions about its function.

By Kaspar Mossman, QB3

QB3 researchers illuminate operation of molecular gateway to the cell nucleus

California | Posted on September 4th, 2010

The NPC, a large protein assembly shaped like a basketball net fringed with tentacles, is the gateway to the cell nucleus, where genetic information is stored. Each cell nucleus contains roughly 2,000 NPCs, embedded in the nuclear envelope. The NPC (which is about 50 nanometers wide) is responsible for all transport into and out of the nucleus. To prevent the contents of the rest of the cell's interior from mixing with that of the nucleus, the NPC discriminates between cargos with great precision.

Several viruses target the NPC to gain entry to the nucleus, and dysfunctional transport between the cytoplasm and the nucleus has been implicated in multiple diseases including cancer.

Scientists have constructed models for the NPC, but how this channel operates and achieves its selectivity has remained a mystery. It is known that, to make it through the NPC, large molecules must bind at least a few receptors called "importins"; whether binding more importins speeds or slows a molecule's passage has been unclear. So, too, has the exact point at which a carrier protein called "Ran" plays a crucial part, substituting one molecule of GTP (a cellular fuel, an analog of the better-known ATP) for one of GDP that the large molecule brings with it when it enters the NPC.

Karsten Weis, a UC Berkeley professor of molecular and cell biology, Jan Liphardt, a UC Berkeley professor of physics, and colleagues conducted advanced imaging experiments that resolved these issues. (Weis and Liphardt are members of QB3.) The research was published September 1st in the journal Nature, in a paper on which Berkeley post-doc Alan Lowe and graduate student Jake Siegel were joint first authors.

Previously, scientists had observed the motion of small molecules (a few nm in diameter), labeled with fluorescent tags, through the NPC. But the rapid transit and faint signal of these molecules resulted in sparse, fuzzy data. Lowe, Siegel, et al. employed "quantum dots", which are about 20 nm in diameter—and hence slower than smaller molecules—and much brighter than conventional fluorophores. The researchers coated the quantum dots with signals recognized by importins. Using a microscopic technique that allowed them to see a flat, thin visual slice through living cells, they watched hundreds of individual dots entering, jiggling around in, being ejected from, and in some cases admitted through, NPCs. The researchers recorded video data and tracked the motion of 849 quantum dots with nanometer precision.

The spaghetti-like paths of the quantum dots, superimposed on one another, revealed that the particles fell into three classes: "early aborts," which were briefly confined and then bounced out; "late aborts," which wandered in and meandered to the inner end of the pore before exiting the way they came; and "successes," which followed much the same paths as the late aborts but were granted entry.

From the paths' erratic meanderings, the researchers deduced that the quantum dots were indeed diffusing randomly, rather than being actively transported. And adding more importins to the dots' coating shortened the transit time, suggesting that importins make incoming cargo more soluble within the NPC rather than binding to interior walls.

The researchers found a particularly interesting result when they withheld the carrier protein Ran from the experiment. Without Ran in the mix, the quantum dots followed exactly the same range of paths as when Ran was present, except that virtually none passed through the NPC.

Considering their path data, the authors drew a model for how the NPC operates. Large cargo is initially captured by the NPC's filament fringe. It then encounters a constriction, through which it can enter a sort of antechamber. Then, in certain cases, Ran exchanges the cargo's GDP for a GTP and it is admitted into the nucleus. Only the final step is irreversible.

"It's an elegant study," says Michael Rout, a professor of cellular and structural biology at The Rockefeller University whose specialty is NPC transport. "If we do eventually understand how the NPC operates at the subtlest level, we could perhaps build filters to select molecules of interest."

Indeed, one of the main new insights is that the NPC's selectivity seems to result from a cascade of filters, each preferring correct cargos, rather than just one very selective step. This helps explain why some things can easily get into the nucleus and other things are excluded. This discovery may have some very practical clinical implications, Liphardt and Weis say. It may enable scientists to develop techniques to efficiently deliver large man-made cargos, such as drug-polymer conjugates and contrast agents, to the nucleus, which contains the genome.

####

About California Institute for Quantitative Biosciences (QB3)
QB3’s mandate is to fulfill its social contract to accelerate discovery and innovation, improving the quality of life in California and beyond.

QB3 harnesses the quantitative sciences of physics and engineering to unify our understanding of biological systems at all levels of complexity, from atoms and molecules to cells, tissues, and entire living organisms. QB3 scientists make discoveries that drive the development of technologies, products, and wholly new industries, ensuring that California remains competitive in the 21st century.

QB3's goals are to fuel the California bioeconomy; to support research and training in quantitative biosciences; and to translate academic research into products and services that benefit society.

For more information, please click here

Copyright © California Institute for Quantitative Biosciences (QB3)

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Nanofiltration Membrane Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Nanozirconia Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Self-Healing Nano Anti-rust Coatings Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Nano Spray Instrument Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Possible Futures

Nanofiltration Membrane Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Nanozirconia Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Self-Healing Nano Anti-rust Coatings Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Nano Spray Instrument Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Academic/Education

Pakistani Students Who Survived Terror Attack to Attend Weeklong “NanoDiscovery Institute” at SUNY Poly CNSE in Albany July 29th, 2015

Deben reports on the use of their CT500 in the X-ray microtomography laboratory at La Trobe University, Melbourne, Australia July 22nd, 2015

JPK reports on the use of SPM in the Messersmith Group at UC Berkeley looking at biologically inspired polymer adhesives. July 21st, 2015

Renishaw adds Raman analysis to Scanning Electron Microscopy at the University of Sydney, Australia July 9th, 2015

Nanomedicine

Heating and cooling with light leads to ultrafast DNA diagnostics July 31st, 2015

European Technology Platform for Nanomedicine and ENATRANS European Consortium Launch the 2nd edition of the Nanomedicine Award: The Award to be presented at BIO-Europe conference in Munich, November 2015 July 30th, 2015

Take a trip through the brain July 30th, 2015

Sol-gel capacitor dielectric offers record-high energy storage July 30th, 2015

Announcements

Nano Spray Instrument Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Nanocellulose Market 2015 - Global Industry Survey, Analysis, Size, Share, Outlook and Forecast to 2020 July 31st, 2015

Heating and cooling with light leads to ultrafast DNA diagnostics July 31st, 2015

Theoretical Physicists at Freie Universität Berlin Develop New Insights into Interface between Classical and Quantum Worlds July 31st, 2015

Quantum Dots/Rods

Quantum networks: Back and forth are not equal distances! July 28th, 2015

Superfast fluorescence sets new speed record: Plasmonic device has speed and efficiency to serve optical computers July 27th, 2015

Engineered hybrid crystal opens new frontiers for high-efficiency lighting: University of Toronto researchers successfully combine 2 different materials to create new hyper-efficient light-emitting crystal July 16th, 2015

Down to the quantum dot: Jülich researchers develop ultrahigh-resolution 3-D microscopy technique for electric fields July 7th, 2015

Nanobiotechnology

Heating and cooling with light leads to ultrafast DNA diagnostics July 31st, 2015

European Technology Platform for Nanomedicine and ENATRANS European Consortium Launch the 2nd edition of the Nanomedicine Award: The Award to be presented at BIO-Europe conference in Munich, November 2015 July 30th, 2015

New computer model could explain how simple molecules took first step toward life: Two Brookhaven researchers developed theoretical model to explain the origins of self-replicating molecules July 28th, 2015

Spintronics: Molecules stabilizing magnetism: Organic molecules fixing the magnetic orientation of a cobalt surface/ building block for a compact and low-cost storage technology/ publication in Nature Materials July 25th, 2015

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project