scholarly journals PADI2-mediated citrullination is required for efficient oligodendrocyte differentiation and myelination

2018 ◽  
Author(s):  
Ana Mendanha Falcão ◽  
Mandy Meijer ◽  
Antonella Scaglione ◽  
Puneet Rinwa ◽  
Eneritz Agirre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Therapeutic Strategy ◽  
Chromatin Accessibility ◽  
Motor Dysfunction ◽  
Peptidylarginine Deiminase ◽  
Oligodendrocyte Differentiation ◽  
Associated Proteins ◽  
Arginine Residues ◽  
Related Proteins

Citrullination, the deimination of arginine residues into citrulline, has been implicated in the aetiology of several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver of pathology, through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutic strategy for MS. Here, in contrast, we show citrullination by peptidylarginine deiminase 2 (PADI2) is required for normal oligodendrocyte differentiation, myelination and motor function. We identify several targets for PADI2, including myelin-related proteins and chromatin-associated proteins, implicating PADI2 in epigenetic regulation. Accordingly, we observe that PADI2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of oligodendrocyte differentiation genes. Moreover, mice lacking PADI2, display motor dysfunction and decreased number of myelinated axons in the corpus callosum. We conclude that citrullination is required for oligodendrocyte lineage progression and myelination and suggest its targeted activation in the oligodendrocyte lineage might be beneficial in the context of remyelination.

Interhemispheric transfer evaluation in multiple sclerosis 1The authors would like to thank Claude-Alain Hauert and Christoph Michel for their assistance in the evaluation of motor tapping and Michel Habib for his suggestions and comments. This work was supported by a grant from the Swiss Society of Multiple Sclerosis.

2000 ◽  
Vol 59 (3) ◽  
pp. 150-158 ◽  
Author(s):  
Nadia Ortiz ◽  
Michael Reicherts ◽  
Alan J. Pegna ◽  
Encarni Garran ◽  
Michel Chofflon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Lexical Decision ◽  
Dichotic Listening ◽  
Neurological Impairment ◽  
Interhemispheric Transfer ◽  
Decision Task ◽  
Swiss Society ◽  
Listening Test ◽  
Relapsing Remitting

Patients suffering from Multiple Sclerosis (MS) have frequently been found to suffer from damage to callosal fibers. Investigations have shown that this damage is associated with signs of hemisphere disconnections. The aim of our study was to provide evidence for the first signs of interhemispheric dysfunction in a mildly disabled MS population. Therefore, we explored whether the Interhemispheric Transfer (IT) deficit is multi-modal and sought to differentiate two MS evolution forms, on the basis of an interhemispheric disconnection index. Twenty-two patients with relapsing-remitting form of MS (RRMS) and 14 chronic-progressive (CPMS) were compared with matched controls on four tasks: a tachistoscopic verbal and non-verbal decision task, a dichotic listening test, cross tactile finger localization and motor tapping. No overall impairment was seen. The dichotic listening and lexical decision tasks were the most sensitive to MS. In addition, CPMS patients' IT was more impaired and was related to the severity of neurological impairment. The different sizes of the callosal fibers, which determine their vulnerability, may explain the heterogeneity of transfer through the Corpus Callosum. Therefore, evaluation of IT may be of value as an index of evolution in MS.

scholarly journals Scanning Electron-Assisted Dielectric Microscopy Reveals Autophagosome Formation by LC3 and ATG12 in Cultured Mammalian Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1834
Author(s):  
Tomoko Okada ◽  
Toshihiko Ogura
Keyword(s):  
Mammalian Cells ◽  
Culture Medium ◽  
Related Gene ◽  
Autophagosome Formation ◽  
Intact Cells ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Difference ◽  
Related Proteins ◽  
Scanning Electron

Autophagy is an intracellular self-devouring system that plays a central role in cellular recycling. The formation of functional autophagosomes depends on several autophagy-related proteins, including the microtubule-associated proteins 1A/1B light chain 3 (LC3) and the conserved autophagy-related gene 12 (Atg12). We have recently developed a novel scanning electron-assisted dielectric microscope (SE-ADM) for nanoscale observations of intact cells. Here, we used the SE-ADM system to observe LC3- and Atg12-containing autophagosomes in cells labelled in the culture medium with antibodies conjugated to colloidal gold particles. We observed that, during autophagosome formation, Atg12 localized along the actin meshwork structure, whereas LC3 formed arcuate or circular alignments. Our system also showed a difference in the distribution of LC3 and Atg12; Atg12 was broadly distributed while LC3 was more localized. The difference in the spatial distribution demonstrated by our system explains the difference in the size of fluorescent spots due to the fluorescently labelled antibodies observed using optical microscopy. The direct SE-ADM observation of cells should thus be effective in analyses of autophagosome formation.

Unraveling the neuroimaging predictors for motor dysfunction in long-standing multiple sclerosis

Neurology ◽  
2015 ◽  
Vol 85 (3) ◽  
pp. 248-255 ◽  
Author(s):  
Marita Daams ◽  
Martijn D. Steenwijk ◽  
Mike P. Wattjes ◽  
Jeroen J.G. Geurts ◽  
Bernard M.J. Uitdehaag ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Motor Dysfunction

scholarly journals Deimination, Intermediate Filaments and Associated Proteins

2020 ◽  
Vol 21 (22) ◽  
pp. 8746
Author(s):  
Julie Briot ◽  
Michel Simon ◽  
Marie-Claire Méchin
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Intermediate Filaments ◽  
Cross Linking ◽  
Post Translational Modification ◽  
Innate And Adaptive Immunity ◽  
Calcium Dependent ◽  
Physiological Processes ◽  
Associated Proteins

Deimination (or citrullination) is a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs). Deimination is involved in physiological processes (cell differentiation, embryogenesis, innate and adaptive immunity, etc.) and in autoimmune diseases (rheumatoid arthritis, multiple sclerosis and lupus), cancers and neurodegenerative diseases. Intermediate filaments (IF) and associated proteins (IFAP) are major substrates of PADs. Here, we focus on the effects of deimination on the polymerization and solubility properties of IF proteins and on the proteolysis and cross-linking of IFAP, to finally expose some features of interest and some limitations of citrullinomes.

Abnormal corpus callosum: a sensitive and specific indicator of multiple sclerosis.

Radiology ◽  
1991 ◽  
Vol 180 (1) ◽  
pp. 215-221 ◽  
Author(s):  
A D Gean-Marton ◽  
L G Vezina ◽  
K I Marton ◽  
G K Stimac ◽  
R G Peyster ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum

scholarly journals A higher proportion of ermin-immunopositive oligodendrocytes in areas of remyelination

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256155
Author(s):  
Intakhar Ahmad ◽  
Stig Wergeland ◽  
Eystein Oveland ◽  
Lars Bø
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Corpus Callosum ◽  
Mouse Model ◽  
Grey Matter ◽  
Early Stage ◽  
Relative Proportion ◽  
Normal Appearing White Matter ◽  
The Brain

Incomplete remyelination is frequent in multiple sclerosis (MS)-lesions, but there is no established marker for recent remyelination. We investigated the role of the oligodendrocyte/myelin protein ermin in de- and remyelination in the cuprizone (CPZ) mouse model, and in MS. The density of ermin+ oligodendrocytes in the brain was significantly decreased after one week of CPZ exposure (p < 0.02). The relative proportion of ermin+ cells compared to cells positive for the late-stage oligodendrocyte marker Nogo-A increased at the onset of remyelination in the corpus callosum (p < 0.02). The density of ermin-positive cells increased in the corpus callosum during the CPZ-phase of extensive remyelination (p < 0.0001). In MS, the density of ermin+ cells was higher in remyelinated lesion areas compared to non-remyelinated areas both in white- (p < 0.0001) and grey matter (p < 0.0001) and compared to normal-appearing white matter (p < 0.001). Ermin immunopositive cells in MS-lesions were not immunopositive for the early-stage oligodendrocyte markers O4 and O1, but a subpopulation was immunopositive for Nogo-A. The data suggest a relatively higher proportion of ermin immunopositivity in oligodendrocytes compared to Nogo-A indicates recent or ongoing remyelination.

scholarly journals THE TIME OF SYNTHESIS AND THE CONSERVATION OF MITOSIS-RELATED PROTEINS IN CULTURED HUMAN AMNION CELLS

1967 ◽  
Vol 34 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Jesse E. Sisken ◽  
Elaina Wilkes
Keyword(s):  
Time Lapse ◽  
Major Effect ◽  
Human Amnion ◽  
Daughter Cells ◽  
Low Concentrations ◽  
Associated Proteins ◽  
A Cell ◽  
Quantitative Analyses ◽  
Related Proteins ◽  
Kinetics Of

p-Fluorophenylalanine (PFPA), an analogue of phenylalanine which may be incorporated into proteins, increases the duration of mitosis. In the present experiments, based upon quantitative analyses of time-lapse cinemicrographic films, brief treatments of cells with PFPA are shown to affect the duration of metaphase in only those cells which enter division during or shortly after treatment. The offspring of cells with prolonged metaphases also tend to have prolonged metaphases. Analyses of the kinetics of the appearance of prolonged metaphases indicate that some protein specifically associated with mitosis is synthesized primarily during a period which corresponds closely to G2. The manner in which the defect is passed on to daughter cells indicates that the protein involved is conserved and reutilized by daughter cells for their subsequent divisions. Comparable experiments performed with low concentrations of puromycin indicate that the major effect of PFPA is due to its incorporation into protein rather than its ability to inhibit protein synthesis. The fact that puromycin-induced effects can also be passed on to daughter cells is interpreted to mean that cells make only specific amounts of some mitosis-associated proteins and that if a cell "inherits" a deficiency in such protein it is not able to compensate for the deficiency.

Sign in / Sign up

Export Citation Format

Share Document