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Immune System Protein May Be Critical In Kidney Disorders And Other Diseases

Date:
October 12, 1999
Source:
Washington University School Of Medicine
Summary:
Evolution has an uncanny way of reusing good blueprints, as researchers recently were reminded when they discovered that a protein involved in immune-cell interactions may be important for kidney function.

St. Louis, Oct. 8, 1999 -- Evolution has an uncanny way of reusing good blueprints, as researchers recently were reminded when they discovered that a protein involved in immune-cell interactions may be important for kidney function.

Andrey S. Shaw, M.D., principal investigator of the research on the CD2-associated protein, says, "Defects in CD2AP may play a critical role in some kidney diseases."

The research is published in today's issue of Science. The first authors of the paper are postdoctoral fellow Neng-Yao Shih, Ph.D., and research associate Jun Li, who both work in Shaw's laboratory at Washington University School of Medicine in St. Louis.

Shaw, associate professor of pathology, led a team of researchers who studied the protein. His group originally cloned the gene as a molecule important for T cell function. The researchers were surprised to find that CD2AP is also specifically expressed in the kidney glomerulus, which filters toxins and other substances from the blood.

The researchers found that mice lacking CD2AP had defective glomeruli and died of renal failure. When they analyzed these mice, they found that CD2AP was expressed in the kidney, mainly in a cell known as a glomerular epithelial cell. The glomerular epithelial cell has a complex shape with foot-like extensions that wrap around capillaries of the glomerulus, forming spaces for the flow of blood filtrate that are called slit diaphragms. In the mice lacking CD2AP, the epithelial cells were damaged and the slit diaphragms were lost.

The mice, developed by Shih and Li, died of kidney failure by the time they were 6 weeks old. The researchers, including co-author Jeffrey H. Miner, Ph.D., assistant professor of medicine and of cell biology and physiology, found progressive damage to the foot-like extensions as early as one week after the mice were born.

How could missing CD2AP have such a dramatic effect on the kidneys? To address this question, Shaw revisited a model concerning CD2AP's potential role in T cells of the immune system. He developed this model with colleagues Mike L. Dustin, associate professor of pathology, and Paul M. Allen, Ph.D., the Robert L. Kroc Professor of Pathology.

T cells defend the body from microbes by interacting with another immune system cell. Shaw previously showed that CD2AP plays an important role in organizing the T cell surface, helping the cell form a molecular bridge with other immune cells.

The molecular bridge forms as a T cell molecule binds to another molecule on the other cell. CD2AP helps position the molecule, CD2, and anchor it at the right place in the membrane. CD2 also serves as a border guard, keeping proteins in separate regions on the T cell surface.

Shaw and his group were struck by the similarities between CD2 and a recently identified protein called nephrin, which is expressed in glomerular epithelial cells. Nephrin, the major component of the slit diaphragm, functions as a molecular bridge between epithelial cells and as a barrier between two distinct surfaces of the epithelial cell. This suggested to Shaw that CD2AP might function by binding to nephrin.

The gene encoding nephrin was cloned last year and identified as the culprit in the most common type of hereditary kidney syndrome, congenital nephrotic syndrome of the Finnish type. Occuring in one of every 10,000 Finns, the syndrome results from lack of nephrin and produces kidney damage, as occurs in Shaw's research animals that lack CD2AP.

This similarity suggests that a defect or lack of CD2AP may be involved in some cases of congenital nephrotic syndrome and other kidney diseases. "This opens up a whole area of inquiry, where we wonder how the slit diaphragm is altered in human kidney diseases and whether a predisposition to kidney failure may be related to genetic defects in the slit diaphragm or kidney epithelial cells," Shaw says.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Immune System Protein May Be Critical In Kidney Disorders And Other Diseases." ScienceDaily. ScienceDaily, 12 October 1999. <www.sciencedaily.com/releases/1999/10/991012075626.htm>.
Washington University School Of Medicine. (1999, October 12). Immune System Protein May Be Critical In Kidney Disorders And Other Diseases. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/1999/10/991012075626.htm
Washington University School Of Medicine. "Immune System Protein May Be Critical In Kidney Disorders And Other Diseases." ScienceDaily. www.sciencedaily.com/releases/1999/10/991012075626.htm (accessed August 30, 2014).

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