where the protein leads
by Robin Arnette

cience has a way of leading researchers down different paths. Carol Otey, assistant professor of cell and molecular physiology, studies cell adhesion and motility and the pathways that regulate the cell shape. Her work is an excellent example of "following where the science leads."

As a postdoctoral fellow in Keith Burridge's lab, Otey discovered a protein that plays a key role in organizing the actin cytoskeleton. Actin is an abundant cellular protein that forms the filaments that give the cell its shape. This new protein, which she named palladin, is involved in actin assembly. "There's no evidence that palladin binds to actin directly. Instead, it binds to multiple things that bind to actin," Otey says.

.: Carol Otey: Her discovery of one protein, palladin, has opened unexpected doors, leading her to study disorders as diverse as cancer and spinal cord injury. "I let the science lead me," she says, "and I end up in unexpected places." Photo by Steve Exum; click to enlarge. :.

Otey studies palladin function in fibroblasts (cells that give rise to connective tissue), neurons (nerve cells), and glia (support cells for neurons). When there is a cellular signal to change shape, palladin protein levels increase. There are a number of situations in which a cell will change shape. For example, tumor cells grow uncontrollably, but within the tumor there is a subpopulation of traveling tumor cells called metastatic cells, which have a different shape. This shape change involves the actin cytoskeleton and palladin. "If we can find a way to specifically interfere with metastasis, cancer would be a treatable disease," Otey says. "We would like to see whether there is a difference in palladin in normal, tumor, and metastatic cells."

n addition to understanding cancer, Otey wants to know what goes wrong when there is an injury to the brain or spinal cord. After a severe injury to the central nervous system (CNS) — the brain and spinal cord — the body experiences a permanent loss of nerve function, but after an injury to the peripheral nervous system (such as a cut in the skin, severing a sensory nerve), the nerves will recover.

Why do nerves in the peripheral nervous system recover better than those in the CNS? One explanation is that when there is an injury to the CNS, neurons are cut and star-shaped glia cells called astrocytes migrate to the area and form a net around the site of injury. If the neuron survives the injury, it is unable to create new connections because it can't punch through the astrocytes. This obstacle is called a glial scar and is a phenomenon of the CNS rather than the peripheral nervous system. This is why the CNS doesn't heal well. "The glial scar involves astrocyte motility and shape change, but the molecular events that control glial scar formation are not understood. If we could understand how these changes arise, we could possibly manipulate the scar and prevent them from forming," Otey says.

Otey's lab uses standard cell biology techniques to manipulate palladin expression in cell culture. She can artificially add palladin by introducing its DNA into cells or inhibit palladin by introducing antisense palladin DNA, which blocks the production of palladin. Using fluorescence microscopy or video microscopy, Otey can observe how the actin cytoskeleton is organized. Otey's observations show that in normal cells, three hours after an injury, palladin levels increase and cluster along the injury site. Also, cells lacking palladin lose their shape.

Because palladin appears to play an important role in metastatic cell movement and glial scar formation, these studies have far-reaching implications for cancer and spinal cord injury research.

Robin Arnette is a postdoctoral fellow at the UNC school of medicine.