Nanotechnology Now







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

‘Oxford Instruments Young Nanoscientist India Award 2015’ to Prof. Arindam Ghosh April 20th, 2015

Nondestructive 3-D Imaging of Biological Cells with Sound April 20th, 2015

Advances in molecular electronics: Lights on -- molecule on: Researchers from Dresden and Konstanz succeed in light-controlled molecule switching April 20th, 2015

Yale-NUS, NUS and UT Austin researchers establish theoretical framework for graphene physics: Making strides towards using graphene to create new electronic devices April 20th, 2015

Possible Futures

A glass fiber that brings light to a standstill: By coupling photons to atoms, light in a glass fiber can be slowed down to the speed of an express train; for a short while it can even be brought to a complete stop April 9th, 2015

Nanotechnology in Medical Devices Market is expected to reach $8.5 Billion by 2019 March 25th, 2015

Nanotechnology Enabled Drug Delivery to Influence Future Diagnosis and Treatments of Diseases March 21st, 2015

Nanocomposites Market Growth, Industry Outlook To 2020 by Grand View Research, Inc. March 21st, 2015

Academic/Education

Iranian Female Professor Awarded UNESCO Medal in Nanoscience April 20th, 2015

JPK reports on the use of the NanoWizard® 3 AFM system at the Hebrew University of Jerusalem April 14th, 2015

UK National Graphene Institute Selects Bruker as Official Partner: World-Leading Graphene Research Facility Purchases Multiple Bruker AFMs April 7th, 2015

SUNY Poly CNSE and Title Sponsor SEFCU Name Capital Region Teams Advancing to the Final Round of the 2015 New York Business Plan Competition March 30th, 2015

Nanomedicine

‘Oxford Instruments Young Nanoscientist India Award 2015’ to Prof. Arindam Ghosh April 20th, 2015

Iranian Female Professor Awarded UNESCO Medal in Nanoscience April 20th, 2015

Happily ever after: Scientists arrange protein-nanoparticle marriage: New biotech method could lead to development of HIV vaccine, targeted cancer treatment April 20th, 2015

Optical resonance-based biosensors designed for medical applications April 18th, 2015

Announcements

Happily ever after: Scientists arrange protein-nanoparticle marriage: New biotech method could lead to development of HIV vaccine, targeted cancer treatment April 20th, 2015

Nondestructive 3-D Imaging of Biological Cells with Sound April 20th, 2015

Advances in molecular electronics: Lights on -- molecule on: Researchers from Dresden and Konstanz succeed in light-controlled molecule switching April 20th, 2015

Yale-NUS, NUS and UT Austin researchers establish theoretical framework for graphene physics: Making strides towards using graphene to create new electronic devices April 20th, 2015

Quantum Dots/Rods

QD Vision Expands Product Line with Two-Millimeter Color LCD Display Optic: Color IQ™ Optic Enables Full-Color Gamut for Ultra-Thin Displays and All-in-One Computers April 16th, 2015

Promising future of quantum dots explored in conference: ‘20 Years of Quantum Dots at Los Alamos’ runs April 12-16 April 13th, 2015

Next important step toward quantum computer: Scientists at the University of Bonn have succeeded in linking 2 different quantum systems March 30th, 2015

Tiny bio-robot is a germ suited-up with graphene quantum dots March 24th, 2015

Nanobiotechnology

Advances in molecular electronics: Lights on -- molecule on: Researchers from Dresden and Konstanz succeed in light-controlled molecule switching April 20th, 2015

Protein Building Blocks for Nanosystems: Scientists develop method for producing bio-based materials with new properties April 17th, 2015

Study shows novel pattern of electrical charge movement through DNA April 14th, 2015

UAB researchers develop a harmless artificial virus for gene therapy April 8th, 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