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Protein Essential for Kidney-to-Bladder Urine Transfer

Tests of a protein's role in the immune system have revealed a surprising connection to a kidney problem that occurs in approximately one percent of all live births//.

"This condition, which is known as functional obstruction, impairs the ureter’s ability to pump urine from the kidney to the bladder," says senior author Wojciech Swat, Ph.D., assistant professor of pathology and immunology. "If untreated, this leaves urine stuck in the kidney, which balloons and becomes at risk of failure."

Swat and colleagues found a similar condition in mice after the gene for a protein known as discs-large homolog 1 (DLGH1) was disabled.

When properly diagnosed, functional obstruction is normally treatable with surgery. But the study also produced tentative evidence that DLGH1 dysfunction may affect long-term risk of kidney failure even after successful treatment.

"We noted about one-third fewer nephrons in mice where this gene had been completely disabled," says co-senior author Jeffrey H. Miner, Ph.D., associate professor of medicine and of cell biology and physiology. "Nephrons are the filtering units of the kidney, and having too few of them can predispose to kidney failure later in life."

The findings, published in the online edition of Proceedings of the National Academy of Sciences, are the first to identify a factor that guides the orientation of smooth muscle cells, which surround the ureter and provide the pumping action that brings urine from the kidney to the bladder. Smooth muscles also play important roles in swallowing, digestion, reproduction, respiration, vision and other biological processes.

Swat and postdoctoral fellow Bénédicte Sammut, Ph.D., originally generated mice lacking DLGH1 to study the protein's role in a structure known as the immune synapse. As conceived by Swat's colleague Andrey Shaw, M.D., the Emil R. Unanue Professor of Immunobiology, the immune synapse is a specialized com
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