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Surprising culprit found in cell recycling defect
Date:2/20/2014

To remain healthy, the body's cells must properly manage their waste recycling centers. Problems with these compartments, known as lysosomes, lead to a number of debilitating and sometimes lethal conditions.

Reporting in the Proceedings of the National Academy of Sciences (PNAS), researchers at Washington University School of Medicine in St. Louis have identified an unusual cause of the lysosomal storage disorder called mucolipidosis III, at least in a subset of patients. This rare disorder causes skeletal and heart abnormalities and can result in a shortened lifespan. But unlike most genetic diseases that involve dysfunctional or missing proteins, the culprit is a normal protein that ends up in the wrong place.

"There is a lot of interest and study about how cells distribute proteins to the right parts of the cell," said senior author Stuart A. Kornfeld, MD, PhD, the David C. and Betty Farrell Professor of Medicine. "Our study has identified one of the few examples of a genetic disease caused by the misplacement of a protein. The protein functions just fine. It just doesn't stay in the right place."

The right place, in this case, is the Golgi apparatus, the cell's protein packaging center. The protein in question phosphotransferase normally resides in the Golgi, where its job is to attach address labels to proteins bound for the lysosome. There are 60 such lysosomal proteins, and all of them must be properly labeled if they are to end up in a lysosome, where they recycle waste.

Kornfeld and his colleagues, including first author Eline van Meel, PhD, postdoctoral research associate, showed that the phosphotransferase protein responsible for adding the address label starts out in the Golgi as it should, but seems to lack the signal to keep it there.

"Under normal circumstances, the phosphotransferase moves up through the Golgi, but then it's recaptured and sent back," Kornfeld said. "Our study sh
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Contact: Julia Evangelou Strait
straitj@wustl.edu
314-286-0141
Washington University School of Medicine
Source:Eurekalert  

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