Kansas City, Mo. (July 15, 2009) – The Stowers Institute’s Abmayr Lab has demonstrated that a fruit fly structure similar to the human site where components in the blood filter into the urine for excretion (the podocyte slit diaphragm) is present in fruit fly cells that detoxify the insect equivalent of blood.

     The work appears in the July 15 issue of Development.

     The team was attempting to determine whether structurally related proteins in flies and humans played similar roles. They focused on whether the removal of unwanted components of fly blood by proteins in nephrocytes is related to the process of filtration through the slit diaphragm of human kidneys by similar proteins.

     “Similar molecules in flies and humans are responsible for forming these structures,” said Susan Abmayr, Ph.D., Associate Investigator and senior author on the paper. “While these findings have also been reported by another group, we have gone on to show that small changes in the structure of the SNS protein — the protein necessary for the proper functioning of the renal filtration barrier in fruit flies — lead to major structural disruptions in the nephrocyte diaphragm. Moreover, elimination of the fly protein Pyd, another conserved slit diaphragm protein, also causes major structural problems.”

     “Our demonstration that fly equivalents of mammalian kidney proteins function in these cells, and that even modest changes in the nephrin-like SNS protein perturb the nephrocyte diaphragm, sets the stage for the use of fruit flies to model the mammalian slit diaphragm in the human kidney,” said Shufei Zhuang, Ph.D., Postdoctoral Research Associate in the Abmayr Lab and co-equal lead author on the publication.

     “Another recent publication demonstrated that mammalian nephrin plays a role in fusion of myoblasts into muscle fibers, a role that we established for the SNS protein in flies several years ago,” said Huanjie Shao, formerly a Postdoctoral Research Associate in the Abmayr Lab and co-equal lead author on the publication. “Together with our recent studies in fly nephrocytes, these studies indicate that the fly and human SNS and nephrin proteins play similar roles in nephrocytes/kidneys and muscles.”

     On the basis of these studies, the team is currently carrying out structure and function studies with SNS in the fly nephrocytes, since structural requirements for SNS are likely to be conserved in nephrin. They are also conducting genetic screens in flies to identify novel molecules associated with nephrocytes and the nephrocyte diaphragm with the hope that these molecules, like those described in this paper, will have human homologs that are critical in the kidney.

     Additional contributing authors from the Stowers Institute include Fengli Guo, Senior Electron Microscopy Specialist; Rhonda Trimble, Electron Microscopy Specialist; and Elspeth Pearce, Research Technician II. Dr. Abmayr is also Associate Professor, Department of Anatomy & Cell Biology at The University of Kansas School of Medicine. Learn more about her work at www.stowers.org/labs/AbmayrLab.asp.

About the Stowers Institute for Medical Research
     Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing, treating, and curing disease. Jim and Virginia Stowers endowed the Institute with gifts totaling $2 billion. The endowment resides in a large cash reserve and in substantial ownership of American Century Investments, a privately held mutual fund company that represents exceptional value for the Institute’s future.