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
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
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."
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 KapoorAbout MD Anderson
Get M. D. Anderson News Via RSS Follow MDAnderson News on Twitter
Scott Merville | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences