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 gla ucoma and in some cases may be involved in the formation of sporadic primar y open-angle glaucoma in humans. To better understand the functions of the MYOC/TIGR protein, its intracellular distribution was investigated using gr een fluorescent protein (GFP) as a marker. The results indicated that the r ecombinant mouse and human Myoc/Tigr-GFP proteins are located in the cytopl asm of the transfected cells in which they colocalize with microtubules. De letion analysis demonstrated that the N-terminal region (positions 1-124 an d 15-138 in the mouse and human proteins, respectively) encoded by exon 1 i s 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 respon sible for the cytoplasmic localization of the protein. However, some of the se mutations may alter the tertiary structure of the protein and subsequent ly modify its interaction with microtubules.