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Cellular Processing of Myocilin

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Title: Cellular Processing of Myocilin
Author(s): 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.
Issue Date: 2014-04-14
Publisher: Public Library of Science
Citation Info: Qiu Y, Shen X, Shyam R, Yue BYJT, Ying H (2014) Cellular Processing of Myocilin. PLoS ONE 9(4): e92845. DOI: 10.1371/journal.pone.0092845
Type: Article
Description: This is a copy of an article published in the PLoS ONE. © 2014 Qiu et al.
URI: http://hdl.handle.net/10027/21083
ISSN: 1932-6203
Sponsor: The present study was supported by grants EY005628, EY018828, and EY001792 (core) from the National Eye Institute, Bethesda, MD, an unrestricted departmental grant from Research to Prevent Blindness, New York, NY, as well as the Research Open Access Publishing (ROAAP) Fund of the University of Illinois at Chicago.
Date Available in INDIGO: 2016-08-29
 

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