Mutations in the gene encoding human
myocilin are associated with some cases of juvenile and
early-onset glaucoma. Glaucomatous mutations prevent
myocilin from being secreted. The analysis of the defects associated with mutations point to the existence of factor(s) in addition to mutations that might be implicated in the development of
glaucoma. In the present paper, we found that interaction of
myocilin with one of the members of the
synuclein family alters its properties, including its ability to be secreted. Results of immunoprecipitation show that
myocilin is a
gamma-synuclein-interacting
protein. Further analysis demonstrated that both
myocilin and
gamma-synuclein are expressed in human TM cells, immortalized rat
ganglion (RGC-5) cells, and HT22 hippocampal neurons. According to Western blotting, in addition to monomeric form with molecular weight 17 kDa
gamma-synuclein is present as higher molecular weight forms ( approximately 35 and 68 KDa), presumably dimer and tetramer.
Myocilin and
gamma-synuclein have partially overlapping perinuclear localization.
Dexamethasone upregulates
myocilin expression in RGC-5 cells and HT22 hippocampal neurons. We found alterations of
myocilin properties as a result of its interaction with
gamma-synuclein. In cultured cells,
gamma-synuclein upregulates
myocilin expression, inhibits its secretion and prevents the formation of high molecular weight forms of
myocilin. Although both
alpha-synuclein and
gamma-synuclein are expressed in HTM cells, only
gamma-synuclein interacts with
myocilin and alters its properties. We conclude that
myocilin and
gamma-synuclein interact and as a result,
myocilin's properties are changed. Since
myocilin and
gamma-synuclein have partially overlapping intracellular localization in cell types that are implicated in
glaucoma development, their interaction may play an important role in
glaucoma.