Protein on the centrosome key to new strategies for stopping cancer growth

A Mayo Clinic discovery about a protein known as Dynamin-2 has thrown conventional wisdom for a loop. Finding the protein on the centrosome, a minute structure near a cell’s nucleus, may lead to new strategies for stopping cancer growth.

The Mayo team, already known for discovering several families of dynamins, this time discovered them -- not on a membrane, as expected -- but on the unlikely centrosome which has no membrane. It was the last place they expected to find them, but the surprise finding offers a new lead in the fight against cancer.

“These findings provide us with a basic understanding of how normal and cancer cells are organized; how they divide and how they might grow and die -- which is an important part of cancer,” says Mark McNiven, Ph.D., the cell biologist who led the Mayo Clinic research team’s investigation. “A lot of cancers, you could argue, don’t grow faster; they just don’t die. So this discovery will improve our understanding of this very relevant cellular process. It promotes understanding the cell at its most basic level, giving us a new layer of detail.”

The research is featured in the April issue of Nature Cell Biology (http://www.nature.com/ncb/). The journal’s editor, Dr. Bernd Pulverer, noted the Mayo results as a novel insight into how cells work. “The Mayo Clinic group has discovered a rather unexpected and surprising connection ... While it remains unclear how exactly Dynamin-2 functions at the centrosome, it clearly localizes to this important structure and it is critical to maintaining an intact centrosome structure. We will follow with great interest further insights into how Dynamin-2 functions in this context, and if this connection serves to integrate signals from the cell surface and membrane trafficking with cell division.”

The newly described relationship between Dynamin-2 and the centrosome poses the intriguing possibility that their partnership connects the cell’s surface and its interior via signals that coordinate and organize cell division. This is compelling because cancer, in essence, is cell division out of control. Taking control of a cell’s “switchboard” — if that’s what this partnership turns out to be — would be a promising potential strategy to pursue in designing new drugs for cancer treatment.

The centrosome is a tiny cellular organ that helps organize chromosomes during cell division. It’s also a signaling center for the cell, and as such is involved in the natural programmed cell death called apoptosis. In yet another role, the centrosome is important in setting up the two poles of the cell during mitosis, when cells segregate their chromosomal material and divide. Both these functions, when disrupted, can cause disease.

Dynamin-2 is an enzyme that helps cells form vesicles used to internalize agents from the cell’s external environment. Through a series of laboratory manipulations of mammalian cells that included disrupting the centrosome, the research team was able to demonstrate that Dynamin-2 is a normal and necessary component of the centrosome. “When we reduced the levels of dynamin in cells, this led to an impairment of the centrosome,” Dr. McNiven explains. The researchers also identified the part of Dynamin-2 that connects it to the centrosome. On the centrosome, they identified the part that recruits and binds Dynamin-2. “As a result of all this investigation, we now know that Dynamin-2 is vital to normal cell structure and organization,” Dr. McNiven says.

The next step is to learn more about the relationship and roles of this partnership. Says Dr. McNiven: “Is the enzymatic activity of Dynamin-2 important in this process? How is it regulated? How does it affect the cell cycle? All these are great questions that will enable us to pursue the ramifications of our discovery.”