Journal article
Cellular Processing of Myocilin
PloS one, Vol.9(4), p.e92845
04/01/2014
DOI: 10.1371/journal.pone.0092845
PMCID: PMC3986080
PMID: 24732711
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.
Details
- Title: Subtitle
- Cellular Processing of Myocilin
- Creators
- Ye Qiu - University of Illinois Urbana-ChampaignXiang Shen - University of Illinois Urbana-ChampaignRajalekshmy Shyam - University of Illinois Urbana-ChampaignBeatrice Y. J. T. Yue - University of Illinois Urbana-ChampaignHongyu Ying - University of Illinois Urbana-Champaign
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(4), p.e92845
- DOI
- 10.1371/journal.pone.0092845
- PMID
- 24732711
- PMCID
- PMC3986080
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library Science
- Number of pages
- 10
- Grant note
- Research to Prevent Blindness, New York, NY; Research to Prevent Blindness (RPB) EY005628; EY018828; EY001792 / National Eye Institute, Bethesda, MD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) Research Open Access Publishing (ROAAP) Fund of the University of Illinois at Chicago
- Language
- English
- Date published
- 04/01/2014
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984949237502771
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