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Chaperone protein subverts removal of glaucoma-causing protein

Date:
October 9, 2012
Source:
University of South Florida (USF Health)
Summary:
The chaperone protein Grp94 can interfere with the clearance of another protein known to cause the glaucoma when mutated, a new study has found. The researchers also demonstrated that a new specific inhibitor of Grp94 facilitates clearance of the genetically-defective protein, called myocilin, from cells.
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FULL STORY

The chaperone protein Grp94 can interfere with the clearance of another protein known to cause the glaucoma when mutated, a new study led by researchers at the University of South Florida has found. Using a cell model, the researchers also demonstrated that a new specific inhibitor of Grp94 facilitates clearance of the genetically-defective protein, called myocilin, from cells.

Reported online this month in JBC (The Journal of Biological Chemistry), the discoveries could lead to a new treatment for some hereditary cases of glaucoma, an eye disease that is a leading cause of blindness, said prinicipal investigator Chad Dickey, PhD, associate professor of molecular medicine at the USF Health Byrd Alzheimer's Institute.

"When mutated, the glaucoma-causing protein becomes toxic to a cell network known as the trabecular meshwork cells that regulate pressure within the eye," Dickey said. "Once these cells die, the ocular pressure increases, causing glaucoma."

Genetic defects of myocilin account for approximately 8 to 36 percent of hereditary juvenile-onset glaucoma and 5 to 10 percent of adult-onset hereditary glaucoma.

The researchers suggest that mutant myocilin, triggered by an interaction with the chaperone Grp94, is highly resistant to degradation, thus clogging the protein quality control pathway and subverting efficient removal of the glaucoma-causing protein. So, the development of targeted therapies to inhibit Grp94 may be beneficial for patients suffering from myocilin glaucoma.

USF researchers from the Department of Molecular Medicine and College of Pharmacy worked on the study, which was supported by the National Institutes of Health and the American Health Assistance Foundation. They collaborated with scientists from the National Eye Institute, Georgia Institute of Technology and University of Kansas.


Story Source:

The above story is based on materials provided by University of South Florida (USF Health). The original article was written by Anne DeLotto Baier. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. Suntharalingam, J. F. Abisambra, J. C. O'Leary, J. Koren, B. Zhang, M. K. Joe, L. J. Blair, S. E. Hill, U. K. Jinwal, M. Cockman, A. S. Duerfeldt, S. Tomarev, B. S. J. Blagg, R. L. Lieberman, C. A. Dickey. Grp94 triage of mutant myocilin through ERAD subverts a more efficient autophagic clearance mechanism. Journal of Biological Chemistry, 2012; DOI: 10.1074/jbc.M112.384800

Cite This Page:

University of South Florida (USF Health). "Chaperone protein subverts removal of glaucoma-causing protein." ScienceDaily. ScienceDaily, 9 October 2012. <www.sciencedaily.com/releases/2012/10/121009121605.htm>.
University of South Florida (USF Health). (2012, October 9). Chaperone protein subverts removal of glaucoma-causing protein. ScienceDaily. Retrieved May 29, 2015 from www.sciencedaily.com/releases/2012/10/121009121605.htm
University of South Florida (USF Health). "Chaperone protein subverts removal of glaucoma-causing protein." ScienceDaily. www.sciencedaily.com/releases/2012/10/121009121605.htm (accessed May 29, 2015).

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