| Deimination restores inner retinal visual function in murine demyelinating disease. | |
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MedLine Citation:
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PMID: 23281397 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Progressive loss of visual function frequently accompanies demyelinating diseases such as multiple sclerosis (MS) and is hypothesized to be the result of damage to the axons and soma of neurons. Here, we show that dendritic impairment is also involved in these diseases. Deimination, a posttranslational modification, was reduced in the retinal ganglion cell layer of MS patients and in a transgenic mouse model of MS (ND4 mice). Reduced deimination accompanied a decrease in inner retinal function in ND4 mice, indicating loss of vision. Local restoration of deimination dramatically improved retinal function and elongation of neurites in isolated neurons. Further, neurite length was decreased by downregulation of deimination or siRNA knockdown of the export-binding protein REF, a primary target for deimination in these cells. REF localized to dendrites and bound selective mRNAs and translation machinery to promote protein synthesis. Thus, protein deimination and dendritic outgrowth play key roles in visual function and may be a general feature of demyelinating diseases. |
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Authors:
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Mabel Enriquez-Algeciras; Di Ding; Fabrizio G Mastronardi; Robert E Marc; Vittorio Porciatti; Sanjoy K Bhattacharya |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-02 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 123 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-04-19 Completed Date: 2013-05-13 Revised Date: 2013-05-29 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 646-56 Citation Subset: AIM; IM |
Affiliation:
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Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE11843 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Amino Acid Sequence Animals Demyelinating Diseases / complications*, genetics, physiopathology* Disease Models, Animal Gene Knockdown Techniques Humans Male Mice Mice, Transgenic Molecular Sequence Data Multiple Sclerosis / complications, physiopathology Nuclear Proteins / antagonists & inhibitors, chemistry, genetics, physiology Protein Processing, Post-Translational RNA-Binding Proteins / antagonists & inhibitors, chemistry, genetics, physiology Retina / pathology, physiopathology* Retinal Ganglion Cells / pathology, physiology Transcription Factors / antagonists & inhibitors, chemistry, genetics, metabolism, physiology Vision Disorders / etiology*, genetics, physiopathology* Vision, Ocular |
| Grant Support | |
ID/Acronym/Agency:
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EB005832/EB/NIBIB NIH HHS; EY014800/EY/NEI NIH HHS; EY015128/EY/NEI NIH HHS; EY016112/EY/NEI NIH HHS; EY019077/EY/NEI NIH HHS; EY02576/EY/NEI NIH HHS; P30 EY014800/EY/NEI NIH HHS; P30 EY014801/EY/NEI NIH HHS; P30 EY014801/EY/NEI NIH HHS; R01 EY019077/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nuclear Proteins; 0/RNA-Binding Proteins; 0/Refbp2 protein, mouse; 0/Transcription Factors |
| Comments/Corrections | |
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