[HTML][HTML] Localization of myocilin to the golgi apparatus in Schlemm's canal cells

ET O'Brien, X Ren, Y Wang - Investigative ophthalmology & …, 2000 - iovs.arvojournals.org
ET O'Brien, X Ren, Y Wang
Investigative ophthalmology & visual science, 2000iovs.arvojournals.org
purpose. Biochemical and genetic evidence suggests that overexpression of or mutations in
myocilin within the cells of the aqueous humor outflow pathway play a significant role in the
development of steroid-induced and several other open-angle glaucomas. As a baseline to
understanding the normal and pathologic function of myocilin, we determined the
subcellular localization of myocilin in steroid-treated human Schlemm's canal endothelial
(SC) cells. methods. SC cells were grown to confluence, treated with dexamethasone for 10 …
Abstract
purpose. Biochemical and genetic evidence suggests that overexpression of or mutations in myocilin within the cells of the aqueous humor outflow pathway play a significant role in the development of steroid-induced and several other open-angle glaucomas. As a baseline to understanding the normal and pathologic function of myocilin, we determined the subcellular localization of myocilin in steroid-treated human Schlemm’s canal endothelial (SC) cells.
methods. SC cells were grown to confluence, treated with dexamethasone for 10 days, and then stained using antibodies against myocilin, tubulin, orβ-COP (a specific golgi protein) or vital stains for endoplasmic reticulum (ER) and golgi. Brefeldin A (BFA) and nocodazol (NZ) were used to disrupt the golgi or microtubules.
results. The authors found that myocilin staining was (a) always centered around the centrosome,(b) very similar to the pattern seen with NBD-ceramide,(c) was disrupted in characteristic ways by BFA and NZ and (d) showed extensive colocalization with β-COP.
conclusions. Results indicate that myocilin is localized to the golgi in SC cells. Such localization is consistent with myocilin being processed for secretion but is also consistent with sequence analysis and other data that suggest that myocilin or myocilin mutations might be targeted to the cytoplasmic face of the golgi, and under some circumstances play a role in or interfere with golgi or vesicle function. How such interference could eventually lead to open angle glaucoma is discussed.
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