A cellular structure discovered 125 years ago and dismissed by many biologists as “cellular garbage” has been found to play a key role in the process of cytokinesis, or cell division, one of the most ancient and important of all biological phenomena.

The discovery of the function of the dozens of proteins-which are necessary for normal cell division-harbored within the midbody of the cell was announced by a team of scientists led by a University of Wisconsin-Madison geneticist in today”s edition of the journal Science. It promises a better understanding of the role of cell division in the growth and development of all organisms and, critically, of abnormal cell division, when the key proteins fail, which can lead to infertility, birth defects, cancer, and neurological problems such as Huntington”s and Alzheimer”s diseases.

“Going from one cell to two, or cytokinesis, is one of the most fundamental of cellular events,” dating to a time when life evolved from single-celled organisms, explains Ahna Skop, an assistant professor of genetics with the UW-Madison College of Agricultural and Life Sciences. “It applies to all species and organisms, and it is fundamental to the growth and development of all life on this planet.”

However, just as cell division is the key to life, failures in it can lead to certain diseases, says Skop. “Several diseases are caused by cells that don”t divide properly, or divide out of control, as in cancer. In addition, proteins that work during cell division may also work in the neurons in our brain or during wound healing, for example. So understanding how cell division works can help us understand how many other specific types of cells function.” With a new understanding of which proteins affect cell division, medical researchers can potentially develop new drugs to prevent cancer and birth defects, treat fertility and neurological disorders, or aid wound healing, among other things.

During the cell cycle, the cell”s genetic information is copied and segregated into two new cells. During normal division, the outer membrane of the cell pinches in, forming two separate cells. Although a very simple event, scientists had not fully understood the mechanisms or identified the proteins involved in separating the two newly formed cells, says Skop.

As a graduate student at UW-Madison in John White”s laboratory, Skop became interested in an ephemeral cellular feature called the midbody, which forms briefly-lasting only a minute in the cells of some species-during cell division. “It was identified over 125 years ago by Walther Flemming, but hadn”t been studied much or paid attention to since,” she explains. “Most people thought it was cellular garbage.”

However, Skop suspected that the midbody was more than an ancient relic with no useful function. She and colleagues used methods developed in the1980s by Ryoko Kuriyama, a UW-Madison post-doctoral researcher at the time and now at the University of Minnesota, and Michael Mullins, now at Catholic University, to isolate midbodies from hamster ovary cells. They then analyzed and identified more than 500 proteins contained in the midbodies. “Proteins are the building blocks of the cell,” explains Skop. “As the cell divides and a new membrane forms, the proteins found during that time in the cell cycle would be crucial elements in understanding how the process works.”

The next step was to inactivate each protein in a developing embryo. If a defect occurred, it would mean that the inactivated protein is essential for normal development. “We used nematodes, which are small roundworms that are cheaper and quicker to use than mammalian cells to assess gene function,” Skop explains. “All but two of the proteins from the mammalian cells were homologous in the nematodes, which allowed us to perform this multi-organismal approach. The fact that the process is highly conserved across two very different species shows how ancient and conserved the process of cell division is.”

The team analyzed 160 key proteins-including 103 not previously known to function in cell division-and found that 58 percent caused cytokinesis defects if they were inactivated. “The problems ranged from cells where chromosomes failed to separate normally, leaving extra DNA in one of the new cells, as is seen in Down”s syndrome, for example, to cells in which the dividing membrane would begin to form normally and would suddenly retract before the cells could separate,” she explains. “Many of the proteins caused a variety of cell division and division-related defects.”

Skop, who also has an appointment with the UW Medical School, conducted some of this work as a post-doctoral researcher at the University of California-Berkeley. Her co-authors on the paper are Hongbin Liu and John Yates from the Scripps Research Institute, Rebecca Heald from UC-Berkeley, and Barbara Meyer from UC-Berkeley and the Howard Hughes Medical Institute. Her work was funded by the National Institutes of Health and the state of Wisconsin.

Additional images of Skop’s work, as well as short movies of normal and abnormal cell division, are available on the UW News website .