Document Detail


Deimination restores inner retinal visual function in murine demyelinating disease.
MedLine Citation:
PMID:  23281397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mabel Enriquez-Algeciras; Di Ding; Fabrizio G Mastronardi; Robert E Marc; Vittorio Porciatti; Sanjoy K Bhattacharya
Related Documents :
16197697 - Audiovisual integration in patients with visual deficit.
7271987 - Some observations on the functional organization of the golden hamster's visual system.
24343377 - Morphological diversity of gabaergic and cholinergic interneurons in the striatal dorso...
24487827 - Selective retinal ganglion cell loss in familial dysautonomia.
16197697 - Audiovisual integration in patients with visual deficit.
9163397 - Inhibitory effects evoked from the anterior hypothalamus are selective for the nocicept...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  646-56     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE11843
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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 EY015128/EY/NEI NIH HHS; R01 EY019077/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/RNA-Binding Proteins; 0/Refbp2 protein, mouse; 0/Transcription Factors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury.
Next Document:  An obligate cell-intrinsic function for CD28 in Tregs.