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Abstract #6296 Published in IGR 3-2
Inefficient processing of an olfactomedin-deficient myocilin mutant: potential physiological relevance to glaucoma
Cabellero M; Borras TBiochemical and Biophysical Research Communications 2001; 282: 662-670
Mutations in TIGR/MYOC (myocilin), a secretory protein of unknown function, have been recently linked to glaucoma. Most known mutations map to the C-terminus, an olfactomedin-like domain. The authors have previously shown that, in contrast to the wild-type, a truncated form of myocilin lacking the olfactomedin domain is not secreted. In this study, they present evidence that the mutant protein is not correctly processed in the endoplasmic reticulum (ER) and accumulates into insoluble aggregates. In addition, they show that the presence of increasing amounts of mutant protein induces a fraction of the soluble, native myocilin to move to the insoluble fraction. Given the importance of such protein aggregates in the etiology of several aging-related diseases, we propose that olfactomedin-defective mutants might contribute to the pathology of glaucoma through a mechanism involving intracellular accumulation of misfolded proteins.
Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA
Classification:
1.2 Population genetics (Part of: 1 General aspects)
