Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Plays Unexpected Role in Embryonic Stem Cells

22.06.2015

What if you found out that pieces of your front door were occasionally flying off the door frame to carry out chores around the house? That’s the kind of surprise scientists at the Salk Institute experienced with their recent discovery that nucleoporins—proteins that act as cellular “doorways” to help manage what goes in and out of a cell’s nucleus—are actually much bigger players in expressing genes than previously thought.

The finding, published June 16,2015 in the journal Genes & Development, shows that nucleoporins play an important role in maintaining embryonic stem cells before they begin to develop into specific tissues. This discovery gives a new understanding to genetic diseases that are caused by mutations in these proteins. One nucleoporin protein in particular has a dramatic—and unanticipated—function in the formation of neurons from stem cells.


Salk Institute

Scientists discovered that a protein called Nup153 (green) control how embryonic stem cells (blue) develop. When Salk scientists deleted Nup153 (left), the cells were free to rapidly begin to turn into the precursors of neurons (marked in red), suggesting a previously unknown role for Nup153.

“We’ve shone a new light on this class of proteins,” says Martin Hetzer, a professor in Salk’s Molecular and Cell Biology Laboratory and senior author of the new paper. “I hope researchers start to accept and realize that nucleoporins are more than just transport proteins.”

Nucleoporins—of which there are about 30 versions—are typically part of nuclear pore complexes, giant structures that connect the inside of a cell’s nucleus to the outer cytoplasm. In 2010, Hetzer’s team first uncovered hints that nucleoporins may also have a role in regulating the timing of when genes inside the nucleus are transcribed into proteins during a cell’s development. But exactly what that role might be was unclear.

In the new work, Hetzer and his colleagues focused on one particular nucleoporin called Nup153, which is known to rapidly move on and off of the nuclear pore complex, suggesting it might be doing something other than providing structural support to the pore.

The researchers turned to mouse embryonic stem cells—cells that have the potential to differentiate into any cell type in the body—and deleted Nup153. They expected that if Nup153 played a key role in cell differentiation, then removing it from stem cells would stop them from differentiating. Instead, the opposite happened.

“The big surprise was that when we took out this gene, the stem cells started to differentiate,” said Hetzer. “And not only did they start to differentiate, but they started to differentiate into neurons.”

Nup153, researchers discovered, put the brakes on certain genes that need to be turned on for stem cells to turn into brain cells. When the brakes are lifted, the stem cells start differentiating.

“This study not only revealed a critical function for nucleoporins in mediating the undifferentiated state of embryonic stem cells by silencing neural genes, but also introduced new mechanistic directions for elucidating the role of these proteins during mammalian development,” says Filipe Jacinto, a postdoctoral researcher in Hetzer’s lab and first author of the paper.

Hetzer suspects that other nucleoporins also have roles in gene expression control, but cautions that the roles could be very different—each nucleoporin, he says, likely targets a different set of genes, and some might activate the genes rather than repress them.

Mutations in many nucleoporin genes has been linked to human diseases and developmental disorders, including some forms of leukemia and inherited heart problems. Until now, Hetzer says, researchers have assumed the mutations led to disease by altering the transport of proteins in and out of a cell’s nucleus. “Now, we’re realizing this is probably not the only explanation,” he says. “Many of those diseases and developmental disorders might actually be caused by the ability of these genes to regulate gene expression programs.”

His lab is planning to follow up with studies on Nup153, and exactly how it’s recruited to genes, as well as investigating the developmental roles of other nucleoporins.

Chris Benner, director of the Integrative Genomics and Bioinformatics Core at the Salk Institute, also contributed to the work.

The work and the researchers involved were supported by grants from the National Institutes of Health and the National Cancer Institute.

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 probes 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, MD, the Institute is an independent nonprofit organization and architectural landmark.

Contact Information
Salk Communications
press@salk.edu

Salk Communications | newswise
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>