EBSCO Logo
Connecting you to content on EBSCOhost
Results
Title

Cellular Processing of Myocilin.

Authors

Qiu, Ye; Shen, Xiang; Shyam, Rajalekshmy; Yue, Beatrice Y. J. T.; Ying, Hongyu

Abstract

Background: Myocilin (MYOC) is a gene linked directly to juvenile- and adult-onset open angle glaucoma. Mutations including Pro370Leu (P370L) and Gln368stop (Q368X) have been identified in patients. In the present study, we investigated the processing of myocilin in human trabecular meshwork (TM) cells as well as in inducible, stable RGC5 cell lines. Methodology/Principal Findings: The turnover and photoactivation experiments revealed that the endogenous myocilin in human trabecular meshwork (TM) cells was a short-lived protein. It was found that the endogenous myocilin level in TM cells was increased by treatment of lysosomal and proteasomal inhibitors, but not by autophagic inhibitor. Multiple bands immunoreactive to anti-ubiquitin were seen in the myocilin pull down, indicating that myocilin was ubiquitinated. In inducible cell lines, the turnover rate of overexpressed wild-type and mutant P370L and Q368X myocilin-GFP fusion proteins was much prolonged. The proteasome function was compromised and autophagy was induced. A decreased PSMB5 level and an increased level of autophagic marker, LC3, were demonstrated. Conclusions/Significance: The current study provided evidence that in normal homeostatic situation, the turnover of endogenous myocilin involves ubiquitin-proteasome and lysosomal pathways. When myocilin was upregulated or mutated, the ubiquitin-proteasome function is compromised and autophagy is induced. Knowledge of the degradation pathways acting on myocilin can help in design of novel therapeutic strategies for myocilin-related glaucoma.

Subjects

MYOCILIN; GENETIC mutation; GLAUCOMA; GENE expression; CHIMERIC proteins

Publication

PLoS ONE, 2014, Vol 9, Issue 4, p1

ISSN

1932-6203

Publication type

Academic Journal

DOI

10.1371/journal.pone.0092845

EBSCO Connect | Privacy policy | Terms of use | Copyright | Manage my cookies
Journals | Subjects | Sitemap
© 2025 EBSCO Industries, Inc. All rights reserved