Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT MD Anderson scientists uncover the nuclear life of actin

25.03.2013
Protein with key job in muscle function moonlights in nucleus to help regulate genes

A key building block of life, actin is one of the most abundant and highly conserved proteins in eukaryotic cells.

First discovered in muscle cells more than 70 years ago, actin has a well-established identity as a cytoplasmic protein that works by linking itself in chains to form filaments. Fibers formed by these actin polymers are crucial to muscle contraction.

So it came as a surprise when scientists discovered actin in the nucleus. Labs have been working for the past few decades to figure out exactly what it's doing there.

A new study published this week in Nature Structural & Molecular Biology reveals that actin has a new and fundamental nuclear function, and that surprisingly, it accomplishes this task in its single-molecule (monomeric) form – not through polymerization.

Senior author of the study Xuetong "Snow" Shen, Ph.D., associate professor in The University of Texas MD Anderson Cancer Center Department of Molecular Carcinogenesis, has been fascinated by the mystery of nuclear actin. In collaboration with researchers from Colorado State University, his lab developed a unique model system to nail down actin's function in the nucleus by studying the actin-containing INO80 chromatin remodeling complex.

In 2000, as a postdoc at NIH in Carl Wu's lab, Shen identified actin as a component of the INO80 complex, adding to the growing list of evidence that actin indeed has a life in the nucleus. However, how actin actually works in the nucleus remains fuzzy due to lack of clear experimental systems.

"Our model system opened up a new opportunity to look in depth at the function of nuclear actin as it relates to gene regulation, genome stability, and ultimately cancer," Snow said.

A nuclear role for monomeric actin

Because yeast have only a single actin gene, the authors reasoned that studying INO80 in yeast cells would allow a direct assessment of the protein's nuclear function. In contrast, mammals have at least six forms of actin coded by separate genes, making their study more difficult.

The researchers used both genetic and biochemical methods to dissect actin's role in the INO80 complex. The INO80 complex normally functions in the nucleus to rearrange chromatin ¬– the intertwined proteins and DNA that are packaged into chromosomes – regulating the expression of many different genes.

The authors found that a mutant form of actin impairs the ability of INO80 to function correctly, implicating actin in the process of chromatin remodeling – an exploding field of research with applications in cancer diagnosis and treatment.

In the cytoplasm, actin functions primarily as a polymer. Cytoplasmic actin is a component of the cytoskeleton and the muscle contractile machinery, and is essential for cell mobility, including cancer metastasis. Actin inside the INO80 complex is arranged in a clever way such that it cannot polymerize; instead, actin's monomeric form appears to interact with chromatin.

"Our study challenges the dogma that actin functions through polymerization, revealing a novel and likely a fundamental mechanism for monomeric nuclear actin," Shen said.

New findings for an ancient complex

Because actin and several of the other INO80 components are so highly conserved, even in human cells, this mechanism likely represents an ancient, fundamental role of actin, which has been preserved through evolution.

Shen's group is now teasing out the exact mechanism by which nuclear actin interacts with chromatin. They also hope to extend the results to human cells and to identify potential ways by which nuclear actin could be involved in cancer.

Chromatin is critical for maintaining the delicate balance between gene activation and repression, Shen said. "Disrupting this regulation can lead to cancer, and it remains to be seen whether nuclear actin has a role in this process."

Lead authors of the study are Prabodh Kapoor, Ph.D., and Mingming Chen, Ph.D., postdoctoral fellows in Shen's lab. Co-authors are Duane David Winkler, Ph.D., and Karolin Luger, Ph.D., of the Department of Biochemistry and Molecular Biology at Colorado State University. Shen, senior author, also is a member of the Center for Cancer Epigenetics at MD Anderson.

The research was funded by grants from the National Cancer Institute (K22CA100017) and the National Institute of General Medical Sciences (RO1GM093104), both of the National Institutes of Health, the Center for Cancer Epigenetics, the Theodore N. Law Endowment for Scientific Achievement at MD Anderson and by MD Anderson's Odyssey postdoctoral program to Kapoor

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For eight of the past 10 years, including 2011, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Get M. D. Anderson News Via RSS Follow MDAnderson News on Twitter

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Climate change: In their old age, trees still accumulate large quantities of carbon

17.08.2017 | Earth Sciences

Modern genetic sequencing tools give clearer picture of how corals are related

17.08.2017 | Life Sciences

Superconductivity research reveals potential new state of matter

17.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>