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 Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>