scholarly journals Studies on myelin-basic-protein methylation during mouse brain development

1986 ◽  
Vol 240 (2) ◽  
pp. 471-479 ◽  
Author(s):  
L P Chanderkar ◽  
W K Paik ◽  
S Kim

The synthesis and methylation in vivo of myelin basic protein (MBP) during the mouse brain development has been investigated. When mice ranging in age from 13 to 60 days were injected intracerebrally with L-[methyl-3H]methionine, the incorporation of radioactivity into MBP isolated from youngest brain was found to be the highest and declined progressively in mature brains. This pattern of radioactivity incorporation was inversely correlated with the total amount of MBP in the brains, suggesting a higher ratio of MBP methylation to synthesis in younger brain. To differentiate the relative rate of protein synthesis and methylation, animals were given intracerebral injections of a L-[methyl-3H]methionine and L-[35S]methionine mixture and the ratio of 3H/35S (methylation index) was determined. The ratios in the isolated MBP fractions were higher than those of ‘acid extracts’ and ‘breakthrough’ fractions, with a maximal ratio in the youngest brain. This high ratio was well correlated with the higher protein methylase I (PMI) activity in younger brains. The MBP fractions were further separated on SDS/polyacrylamide-gel electrophoresis into several species with apparent Mr ranging from 32,400 to 14,500. The results indicated that each protein species accumulated at a characteristic rate as a function of age. The high-Mr (32,400) species was predominant in younger brain, whereas the smaller MBP was the major species in older brain tissue. The importance of this developmental pattern of MBP synthesis and methylation is discussed in relation to PMI activity.

1992 ◽  
Vol 287 (3) ◽  
pp. 929-935 ◽  
Author(s):  
N Rawal ◽  
Y J Lee ◽  
W K Paik ◽  
S Kim

The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN′G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found in MBP; however, their relative concentrations varied significantly with the age of the animal. The amounts of MeArg and Me2(sym)Arg in MBP increased as a function of the age of the brain, whereas that of Me2(asym)Arg decreased. MBP from early-myelinating mouse brain was shown to contain a high proportion of Me2(asym)Arg, which was hardly detectable in older brain MBP. This derivative, Me2(asym)Arg, was also absent from MBP embedded in the most compact multilamellar myelin, but was present in MBP in the least compact myelin (P3B). Comparing the extent of total methylation in vivo (sum of all three arginine derivatives), MBP extracted from less-compact myelin (P3A and P3B) showed a level approx. 40% higher than that from compact myelin. MBPs isolated from dysmyelinating mutant mouse brains, such as jimpy (jp/y) and quaking (qk/qk), contained a much higher level of Me2(asym)Arg relative to the other two methyl derivatives and also in comparison with those levels in the mother brain MBP. SDS/PAGE analysis of MBPs extracted from the mutant (both jp/y and qk/qk) as well as young normal (6-13 days old) mouse brains indicated the presence of a high-molecular-mass isoform of MBP (about 32 kDa), but this isoform was not found in adult brains. These results therefore indicate that structural integrity of myelin membrane in which MBP is embedded appears to play a pivotal role in determining the extent and the kind of Me2Arg formation in MBP at the post-translational level.


1984 ◽  
Vol 98 (3) ◽  
pp. 1090-1097 ◽  
Author(s):  
D G Drubin ◽  
D Caput ◽  
M W Kirschner

Tau protein is a collection of closely related polypeptides that associate with microtubules in vivo and stimulate their assembly in vitro. Using an affinity-purified antiserum against bovine brain tau protein, we found that the number and amount of tau polypeptides changes dramatically during mouse brain development. The different forms appear to result from changes in tau mRNA since in vitro translation products reflect the qualitative and quantitative changes found in vivo. To study the mRNA and genomic complexity of tau protein, we used tau mRNA, purified from polysomes with tau antiserum, to isolate embryonic mouse tau complementary DNA clones. With these probes we have determined that embryonic tau protein is translated from a 6-kb mRNA that persists throughout brain development.


2020 ◽  
Author(s):  
Amandine Bery ◽  
Olivier Etienne ◽  
Laura Mouton ◽  
Sofiane Mokrani ◽  
Christine Granotier-Beckers ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.


2004 ◽  
Vol 17 (8) ◽  
pp. 613-619 ◽  
Author(s):  
Youssef Zaim Wadghiri ◽  
Jeffrey A. Blind ◽  
Xiaohong Duan ◽  
Clement Moreno ◽  
Xin Yu ◽  
...  

2018 ◽  
Vol 128 ◽  
pp. 50-57 ◽  
Author(s):  
Hidenori Ito ◽  
Makoto Mizuno ◽  
Kei Noguchi ◽  
Rika Morishita ◽  
Ikuko Iwamoto ◽  
...  

2014 ◽  
Vol 449 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Xiang Ao ◽  
Yunlai Liu ◽  
Maolin Qin ◽  
Chengren Li ◽  
Xingshu Chen ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document