New Protein A Key To Cell Shape And Movement

The newly identified protein, palladin, is being explored for its influence on a number of biological processes including the invasive spread of cancer, wound healing, brain development, and the implantation of the embryo in the uterus.

"I think it may be critically involved in even more biological functions," said Carol A. Otey, PhD, assistant professor of cell and molecular physiology at UNC-CH School of Medicine.

A report of the discovery, co-authored by Mana M. Parast, PhD, of the University of Virginia, will be published in the August 7 issue on the Journal of Cell Biology.

Otey named the new protein after Andrea Palladio, the influential 16th century architect. Palladin appears to be very involved in the architecture of cells, specifically via the actin cytoskeleton, a polymer protein complex that provides much of the basis for cell shape.

"Cells have a shape that is related to their function," Otey explains. "A good example of specialized cell shape is the neuron. They must be very long and skinny to allow the nervous system to function. Another example is epithelial cells [including skin cells] which bind tightly to one another to form a continuous sheet."

According to Otey's findings, palladin belongs to a small group of cytoskeletal adhesion proteins that seem to provide molecular 'glue' for maintaining cellular shape and for the attachment of cells to one another via their plasma membranes. For example, fibroblasts are spindle-shaped cells involved in connective tissue, collagen formation and are also crucial to wound healing. In these cells, palladin is very concentrated near attachment points to the plasma membrane.

On the other hand, palladin is absent, not expressed, in some undifferentiated cells; that is, in cells which haven't achieved their genetically predetermined shape. Thus, the protein is absent in precursor stem cells. "So this indicates that palladin plays a role in forming the new cytoskeleton of cells that are beginning to differentiate and take on their specialized shape," she said.

According to Otey, an exciting thing about palladin is it's presence in different forms, different molecular weights. "In many different types of cells, one form of palladin may be necessary for tight adhesion and another for migration, or movement," she said. The Carolina scientist notes that a heavier form of palladin is more highly present, or expressed, in metastatic cancer cells - tumor cells that spread beyond their point of origin.

"It is also this form of palladin we see highly expressed in the early placenta, which of course is an 'invasive' organ," said Otey.

And it is during the first half of the ovulatory cycle that the womb prepares for embryo implantation by undergoing very dramatic changes in cell shape. A palladin form of greater molecular mass occurs during that time and then diminishes later in the cycle. "So again its expression correlates with these very dynamic structural changes," Otey noted. "That's why we think there's clearly a role for palladin from the point of view of the embryo and the point of view of the placenta."

Still, as the researcher points out, exactly what the new protein does in normal cells and in cancer cells remains to be clarified further. Her laboratory is seeking answers.

"In this first paper we describe the discovery of this protein. It's basically a birth announcement," Otey said. "All of the subsequent studies will be built on this. In the pipeline we have projects related to neuroscience, orthopedic research, developmental biology, including embryo implantation, and we're studying palladin in cancer metastasis. I think in the next couple of years we'll see results that are more specific to public health concerns."

This research is supported by grants from the National Institutes of Health.