Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain.

Abstract

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, we 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. We 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 h post-infection. Based on these findings, we 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.

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@article{Caballero2000AlteredSO, title={Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain.}, author={Montserrat Caballero and Laura Leigh S Rowlette and Terete Borr{\'a}s}, journal={Biochimica et biophysica acta}, year={2000}, volume={1502 3}, pages={447-60} }