Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nuclear Pores Call on Different Assembly Mechanisms at Different Cell Cycle Stages

11.06.2010
Nuclear pores are the primary gatekeepers mediating communication between a cell's nucleus and its cytoplasm. Recently these large multiprotein transport channels have also been shown to play an essential role in developmental gene regulation. Despite the critical role in nuclear function, however, nuclear pore complexes remain somewhat shadowy figures, with many details about their formation shrouded in mystery.

Now a team of investigators from the Salk Institute for Biological Studies has illuminated key differences in the mechanisms behind nuclear pores formed at two distinct stages in the cell cycle. Their findings, to be published in the June 12 issue of Cell, may provide insights into conditions such as cancer, developmental defects, and sudden cardiac arrest.

Nuclear pores, which are built from 30 different proteins, assemble during interphase, the period when the nucleus expands and replicates its DNA, and following mitosis, when the nuclear membrane reforms around the segregated chromosomes to create two identical nuclei.

But, explains Martin Hetzer, Ph.D., Hearst Endowment associate professor in Salk's Molecular and Cell Biology Laboratory, who led the study, there has been a longstanding question about whether assembly pathways at the distinct cell cycle stages use different or similar mechanisms. "Interphase assembly is different from post-mitotic assembly in that the nuclear membrane is fully formed around chromatin," he says, "whereas post-mitotic assembly occurs into the reforming nuclear membrane. So the topology of the nuclear membrane is very different during these two cell cycle stages."

While some aspects of post-mitotic assembly were known, almost nothing was understood about how assembly of the pores occurs during interphase, when the cell doubles the number of nuclear pores to provide sufficient levels of NPC components for the two daughter cells. A parallel process takes place during differentiation of an oocyte, when millions of nuclear pore components are integrated into the nuclear membrane of the egg cell, so any findings about interphase assembly could also be relevant to embryonic development.

"We were able to show for the first time that there are two distinct mechanisms behind how these large protein complexes assemble to accommodate cell cycle-dependent differences in nuclear membrane topology," says Hetzer.

The team identified a key difference in how the Nup107/160 complex, which is essential for NPC formation, is targeted to new assembly sites in the NE. Surprisingly, one of the complex members, Nup133, is directed to the pore assembly site via a completely novel mechanism that involves sensing of the nuclear membrane's curvature. "The sensor was identified in a bioinformatics screen, and it was not known whether it was really functional in vivo," says co-first author Christine Doucet, Ph.D., a postdoctoral fellow in Hetzer's lab. "But we thought it would fit in with the topology of the nuclear membrane and the sites of the new nuclear pore complexes because they are highly curved. So if the sensor was playing a role in assembly, it was a really neat way to coordinate the assembly of all the components at the right position and the right time."

The second difference the group discovered is that in post-mitotic assembly, but not during interphase, a protein called ELYS played a key role in directing the NUP107/160 complex, which is critical to the formation of pores, to the assembly sites. In contrast, the transmembrane Nup POM121, is specifically required for interphase assembly.POM121 is the earliest known protein at pore assembly sites yet how it is directed there is still under investigation.

"We knew both proteins were essential for pore assembly in different ways, but we didn't know how," says co-first author Jessica Talamas, also a postdoctoral fellow in Hetzer's lab. "There was a discrepancy in the literature about POM121, so we were trying to figure out what was going on. It was one of those lightbulb moments, we were looking at the data and realized that POM121 was only required for interphase assembly, and then everything just made sense."

Because these processes are at work in every cell that divides, the study is especially germane to one of the big questions in the field: how the number of nuclear pores is regulated. It's a question with multiple ramifications. Nuclear pore numbers are misregulated in cancer cells, for example, so the findings have applications in cancer research. In addition, because neurons require a large number of nuclear pores, evidence is mounting that defects in nuclear pore assembly are linked to developmental defects in the central nervous system. Assembly defects during development have also been implicated in conditions such as sudden cardiac arrest.

"In establishing differences between the two assembly pathways, the findings have provided the first glimpse of a mechanistic understanding," Hetzer says.

This study was supported by a grant from the National Institutes of Health.

About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.

Gina Kirchweger | Newswise Science News
Further information:
http://www.salk.edu

Further reports about: Biological Studies NPC Nobel Prize Nuclear POM121 cardiac arrest cell cycle cell death pores

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>