Phase Separation of Myelin Proteins in Triton X-114: Differential Behavior of Myelin Basic Protein in Purified Myelin and in Cultured Oligodendrocytes

1989 ◽  
Vol 11 (3) ◽  
pp. 179-187 ◽  
Author(s):  
Philippe Bürgisser ◽  
Jean-Marie Matthieu
Keyword(s):  
Phase Separation ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Myelin Proteins ◽  
Differential Behavior ◽  
Triton X

Two-dimensional gel electrophoresis of human brain proteins. V. Non-equilibrium gel electrophoresis, with detection of a myelin basic protein mutation--MBL-Duarte.

1982 ◽  
Vol 28 (4) ◽  
pp. 813-818 ◽  
Author(s):  
D E Comings ◽  
A Pekkula-Flagan
Keyword(s):  
Human Brain ◽  
Myelin Basic Protein ◽  
Gel Electrophoresis ◽  
Basic Protein ◽  
Myelin Proteins ◽  
Two Dimensional Gel Electrophoresis ◽  
Brain Proteins ◽  
Basic Proteins ◽  
A Charge ◽  
Non Equilibrium

Abstract To examine the basic human brain proteins, we subjected 9 mmol/L urea extracts to non-equilibrium gel electrophoresis. The pattern observed differs distinctly from that with equilibrium gel electrophoresis. With this technique, the myelin proteins (myelin basic protein, proteolipids, and basic Wolfgram proteins) and many other unindentified major basic proteins can be demonstrated. The myelin basic proteins occur as two major polypeptides of different charge and slightly different molecular mass, indicating the action of at least two genes. The proteolipid proteins occur as a long series of charge isomers, suggesting multiple genes or extensive post-transcriptional modification. In one patient with schizophrenia, a charge-change mutation of the larger myelin basic protein (MBL) was observed and is termed "MBL-Duarte."

Phase separation of acidic and neutral phospholipids induced by human myelin basic protein

Biochemistry ◽  
1977 ◽  
Vol 16 (25) ◽  
pp. 5420-5426 ◽  
Author(s):  
J. M. Boggs ◽  
M. A. Moscarello ◽  
D. Papahadjopoulos
Keyword(s):  
Phase Separation ◽  
Myelin Basic Protein ◽  
Basic Protein

scholarly journals Transcriptional Regulators of the Golli/Myelin Basic Protein Locus Integrate Additive and Stealth Activities

2020 ◽  
Author(s):  
Hooman Bagheri ◽  
Hana Friedman ◽  
Kathy Siminovitch ◽  
Alan Peterson
Keyword(s):  
Nervous System ◽  
Myelin Basic Protein ◽  
Schwann Cells ◽  
Basic Protein ◽  
Cell Types ◽  
Myelin Proteins ◽  
Transcriptional Unit ◽  
Individual Autonomy ◽  
Specific Gene ◽  
Regulatory Sequences

ABSTRACTMyelin is composed of plasma membrane spirally wrapped around axons and compacted into dense sheaths by myelin associated proteins. In the central nervous system (CNS), myelin is elaborated by neuroepithelial derived oligodendrocytes and in the peripheral nervous system (PNS) by neural crest derived Schwann cells. While some myelin proteins are unique to only one lineage, myelin basic protein (Mbp) is expressed in both. Overlapping the Mbp gene is Golli, a transcriptional unit that is expressed widely both within and beyond the nervous system. A super-enhancer domain within the Golli/Mbp locus contains multiple enhancers shown previously to drive reporter construct expression specifically in oligodendrocytes or Schwann cells. In order to determine the contribution of each enhancer to the Golli/Mbp expression program and examine if interactions among these enhancers occur, we derived mouse lines in which enhancers were deleted, either singly or in different combinations, and relative mRNA accumulation was measured at key stages of development. Although super-enhancers have been shown to facilitate interaction among their component enhancers, the enhancers investigated here demonstrated functions that were largely additive. However, enhancers demonstrating autonomous activity strictly in one cell lineage, when missing, were found to significantly reduce output in the other thus revealing cryptic “stealth” activity. Further, Golli accumulation in all cell types investigated was markedly and uniformly attenuated by the absence of a key oligodendrocyte enhancer. Our observations expose a novel level of enhancer interaction and are consistent with a model in which enhancer-mediated DNA looping underlies higher-order Golli/Mbp regulatory organization.AUTHOR SUMMARYThe control of transcription is mediated through regulatory sequences that engage in a lineage and developmentally contextual manner. The Golli/Mbp locus gives rise to several mRNAs and while Mbp mRNAs accumulate exclusively in the two glial cell types that elaborate myelin, Golli mRNAs accumulate in diverse cell types both within and beyond the nervous system. To determine how the different Golli/Mbp enhancers distribute their activities and to reveal if they operate as autonomous agents or have functionally significant interactions with each other we derived multiple enhancer knock-out lines. Comparing the developmental accumulation of Mbp and Golli mRNAs revealed that the autonomous targeting capacity of multiple enhancers accurately predicted their in-situ contributions. Also, they acted in a largely additive manner indicating significant individual autonomy that can be accounted for by a simple chromatin looping model. Unexpectedly, we also uncovered cryptic “stealth” activity emanating from these same enhancers in lineages where they show no autonomous targeting capacity thus providing new insight into the control of lineage specific gene expression.

scholarly journals Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Samantha K. Barton ◽  
Jenna M. Gregory ◽  
Bhuvaneish T. Selvaraj ◽  
Karina McDade ◽  
Christopher M. Henstridge ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Myelin Basic Protein ◽  
Protein Misfolding ◽  
Basic Protein ◽  
Neuronal Loss ◽  
Myelin Proteins ◽  
Structural Level ◽  
Sporadic Als ◽  
Als Patients ◽  
Lateral Sclerosis

Pathological hallmarks of amyotrophic lateral sclerosis (ALS), including protein misfolding, are well established in oligodendrocytes. More recently, an RNA trafficking deficit of key myelin proteins has been suggested in oligodendrocytes in ALS but the extent to which this affects myelination and the relative contribution of this to disease pathogenesis is unclear. ALS autopsy research findings showing demyelination contrasts with the routine clinical-pathological workup of ALS cases where it is rare to see white matter abnormalities other than simple Wallerian degeneration secondary to widespread neuronal loss. To begin to address this apparent variance, we undertook a comprehensive evaluation of myelination at an RNA, protein and structural level using human pathological material from sporadic ALS patients, genetic ALS patients (harboring C9orf72 mutation) and age- and sex-matched non-neurological controls. We performed (i) quantitative spatial profiling of the mRNA transcript encoding myelin basic protein (MBP), (ii) quantification of MBP protein and (iii) the first quantitative structural assessment of myelination in ALS post-mortem specimens by electron microscopy. We show no differences in MBP protein levels or ultrastructural myelination, despite a significant dysregulation in the subcellular trafficking of MBP mRNA in ALS patients compared to controls. We therefore confirm that whilst there are cell autonomous mRNA trafficking deficits affecting oligodendrocytes in ALS, this has no effect on myelin structure.

Transcription of myelin basic protein promoted by regulatory elements in the proximal 5’ sequence requires myelinogenesis

1996 ◽  
Vol 2 (3) ◽  
pp. 125-132 ◽  
Author(s):  
B Stankoff ◽  
C Demerens ◽  
C Goujet-Zalc ◽  
M Monge ◽  
F Peyron ◽  
...  
Keyword(s):  
Myelin Basic Protein ◽  
Reporter Gene ◽  
Transcriptional Activation ◽  
Basic Protein ◽  
Transgenic Animals ◽  
Promoter Sequence ◽  
Regulatory Elements ◽  
Myelin Proteins ◽  
Proximal Promoter ◽  
Myelin Formation

Myelination in the central nervous system requires synthesis by oligodendrocytes of enormous amounts of lipids and proteins for incorporation in the developing myelin membranes. To approach the regulatory events coordinating the transcriptional activation of the genes that encode myelin proteins, we examined control of the myelin basic protein (MBP) locus. MBP plays a major role in myelin compaction. During development, MBP is already expressed in mature non-myelinating oligodendrocytes. Here we show that, in transgenic animals in which the E. coli lacZ reporter gene is under the control of increasingly large portions (256, 1900 and 3200 bp) of the MBP promoter, 5’ of the initiation of transcription site, reporter gene expression was initiated after myelin formation had started. This delayed expression of the transgene compared to MBP, strongly suggests that premyelinating expression is dependent on regulatory elements located outside of the 3200 bp sequence studied, while expression occurring at the time of myelin formation is dependent on the proximal promoter sequence.

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