Nanotechnology Now

Our NanoNews Digest Sponsors



Heifer International

Wikipedia Affiliate Button


android tablet pc

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

Iranian Researchers Synthesize Stable Ceramic Nanopowders at Room Temperature September 20th, 2014

Arrowhead to Present at BioCentury's NewsMakers in the Biotech Industry Conference September 19th, 2014

SouthWest NanoTechnologies (SWeNT) Receives NIST Small Business Innovation Research (SBIR) Phase 1 Award to Produce Greater than 99% Semiconducting Single-Wall Carbon Nanotubes September 19th, 2014

Toward optical chips: A promising light source for optoelectronic chips can be tuned to different frequencies September 19th, 2014

Possible Futures

Air Force’s 30-year plan seeks 'strategic agility' August 1st, 2014

IBM Announces $3 Billion Research Initiative to Tackle Chip Grand Challenges for Cloud and Big Data Systems: Scientists and engineers to push limits of silicon technology to 7 nanometers and below and create post-silicon future July 10th, 2014

Virus structure inspires novel understanding of onion-like carbon nanoparticles April 10th, 2014

Local girl does good March 22nd, 2014

Academic/Education

Biosensors Get a Boost from Graphene Partnership: $5 Million Investment Supports Dozens of Jobs and Development of 300mm Fabrication Process and Wafer Transfer Facility September 18th, 2014

Malvern technology delivers Malvern reliability in multi-disciplinary lab at Queen Mary University London September 9th, 2014

State University of New York Trustees Unanimously Approve SUNY Polytechnic Institute (SUNY Poly) as New Name for Merged SUNY CNSE / SUNYIT September 9th, 2014

New Vice President Takes Helm at CNSE CMOST: Catherine Gilbert To Lead CNSE Children’s Museum of Science and Technology Through Expansion And Relocation August 29th, 2014

Nanomedicine

Arrowhead to Present at BioCentury's NewsMakers in the Biotech Industry Conference September 19th, 2014

The Pocket Project will develop a low-cost and accurate point-of-care test to diagnose Tuberculosis: ICN2 holds a follow-up meeting of the Project on September 18th - 19th September 18th, 2014

New non-invasive technique could revolutionize the imaging of metastatic cancer September 17th, 2014

Recruiting bacteria to be technology innovation partners: September 17th, 2014

Announcements

Iranian Scientists Separate Zinc Ion at Low Concentrations September 20th, 2014

Arrowhead to Present at BioCentury's NewsMakers in the Biotech Industry Conference September 19th, 2014

SouthWest NanoTechnologies (SWeNT) Receives NIST Small Business Innovation Research (SBIR) Phase 1 Award to Produce Greater than 99% Semiconducting Single-Wall Carbon Nanotubes September 19th, 2014

Toward optical chips: A promising light source for optoelectronic chips can be tuned to different frequencies September 19th, 2014

Quantum Dots/Rods

Nano-pea pod model widens electronics applications: A new theoretical model explains how a nanostructure, such as the nano-pea pod, can exhibit localised electrons September 4th, 2014

Interaction between Drug, DNA for Designing Anticancer Drugs Studied in Iran August 17th, 2014

NANOPARTICLES INDIA August 8th, 2014

Researchers create quantum dots with single-atom precision June 30th, 2014

Nanobiotechnology

Arrowhead to Present at BioCentury's NewsMakers in the Biotech Industry Conference September 19th, 2014

CiQUS researchers design an artificial nose to detect DNA differentiation with single nucleotide resolution September 18th, 2014

Biosensors Get a Boost from Graphene Partnership: $5 Million Investment Supports Dozens of Jobs and Development of 300mm Fabrication Process and Wafer Transfer Facility September 18th, 2014

Recruiting bacteria to be technology innovation partners: September 17th, 2014

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







© Copyright 1999-2014 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE