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Abstract #15829 Published in IGR 2-3
Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain
Caballero M; Rowlette LL; Borras TBiochimica et Biophysica Acta 2000; 15: 447-460
TIGR/MYOC, a novel 504 amino acids (aa) protein of unknown function, has recently been linked to glaucoma. The protein is both intra- and extracellular and most known mutations map to its C-terminus, an olfactomedin-like domain. To investigate the properties of a TIGR/MYOC peptide lacking this important domain, the authors constructed a replication-deficient adenovirus with the first 344 aa and over-expressed the truncated protein in primary human trabecular meshwork cells and perfused human anterior segment cultures. The truncated mutant contains the entire N-terminus plus 98 aa of the olfactomedin-like domain. They found that the delivered truncated mutant accumulates inside the cell, reduces secretion of endogenous TIGR/MYOC and induces an increase in outflow facility at 48 hours post-infection. Based on these findings, the authors hypothesize that TIGR/MYOC might have a dual role in trabecular meshwork function. This dual role might be that of an intracellular modulator of vesicular transport as well as that of a secreted protein involved in extracellular matrix conformation. Both functions could have a direct effect in maintaining aqueous humor outflow facility.
Dr. M. Caballero, Department of Ophthalmology, Duke University Medical Center, Wadsworth Building, Erwin Road, P.O. Box 3802, 27710, Durham, NC, USA
Classification:
1.2 Population genetics (Part of: 1 General aspects)