Identification of the region in the N-terminal domain responsible for the cytoplasmic localization of Myoc/Tigr and its association with microtubules.

Mutations in the MYOC/TIGR gene are associated with juvenile open-angle glaucoma and in some cases may be involved in the formation of sporadic primary open-angle glaucoma in humans. To better understand the functions of the MYOC/TIGR protein, its intracellular distribution was investigated using green fluorescent protein (GFP) as a marker. The results indicated that the recombinant mouse and human Myoc/Tigr-GFP proteins are located in the cytoplasm of the transfected cells in which they colocalize with microtubules. Deletion analysis demonstrated that the N-terminal region (positions 1-124 and 15-138 in the mouse and human proteins, respectively) encoded by exon 1 is critical for the cytoplasmic localization of Myoc/Tigr. Most of the known mutations in the human MYOC/TIGR gene implicated in juvenile and sporadic primary open-angle glaucoma formation are located outside the region responsible for the cytoplasmic localization of the protein. However, some of these mutations may alter the tertiary structure of the protein and subsequently modify its interaction with microtubules.