Study uncovers actin's action in the nucleus, a break in protein's puzzling case
Actin is a protein that has been long known to work by linking itself into chains to form filaments. Providing rigidity to the cell, actin filaments are involved in a host of processes including muscle contraction, cell mobility and cell division. The protein does this job outside of the nucleus, in the cytoplasm.
When actin was first discovered in the cell's nucleus several decades ago, it was dismissed as a contaminant. But since then a growing list of studies have supported a nuclear role for the protein, and scientists have been stumped as to what exactly it's doing there.
At long last, one of actin's key nuclear functions was uncovered. The study was published this week in the Journal Nature Structural & Molecular Biology.
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, developed a unique model system to nail down actin's function in the nucleus: the actin-containing INO80 chromatin remodeling complex in yeast cells.
"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.
The authors found that a mutant form of actin impairs the ability of INO80 to function correctly, implicating nuclear actin in the process of chromatin remodeling - a mechanism that helps regulate the expression of genes.
Cancer studies have increasingly focused on chromatin -- the intertwined proteins and DNA that are packaged into chromosomes -- because of its ability to regulate genes important for either activating or inhibiting tumorigenesis.
Surprisingly, Shen's lab found that actin inside the INO80 complex is arranged in such a way that it can't link up with itself to form filaments. Instead, the protein functions singly, as a monomer.
"Our study challenges the dogma that actin functions through polymerization, revealing a novel and likely a fundamental mechanism for monomeric nuclear actin," Shen said.