Localization of basic proteins in human myelin

McLaurin, JoAnne; Ackerley, Cameron; Moscarello, Mario A.

doi:10.1002/jnr.490350605

Cited by 38 publications

(31 citation statements)

References 28 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1b). McLaurin et al (20) found that the intermembrane bridging of MBP is reduced as the net positive charge drops from 20 (known as the C1 isomer) to 10 (the C8 isomer). For our studies we chose the most abundant MBP C1 isomer (of the 18.5-kDa isoform), purified and lipid-free, as described and characterized in ref.…”

Section: Methodsmentioning

confidence: 99%

Synergistic interactions of lipids and myelin basic protein

Doudevski

Wood

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid ''hole-filler,'' effectively preventing defect holes from developing. From our protein-mediated-adhesion and forcedistance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the ''important ones'' may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.lipid-protein interactions ͉ myelin membrane structure ͉ membrane adhesion ͉ membrane regeneration͞healing ͉ demyelinating diseases T his communication addresses the general question of the molecular interactions that determine the structure and stability of membranes that are stabilized by bridging proteins, with the myelin sheath of the central nervous system (CNS) being taken as a prime example of this type of structure. The myelin sheath is formed by extensions of oligodendrocyte cell membranes that wrap around the axon to form a cylindrical scroll a few tens of micrometers in diameter (1, 2). The sheath consists of repeat units of ''double'' bilayers separated by 3-to 4-nm-thick aqueous layers that alternate between the cytoplasmic and extracellular spaces (2). Seventy to 80% of the dry weight of myelin consists of lipids, a proportion that is significantly higher than in most other cell membranes. There are two major proteins: myelin basic protein (MBP), which spans the aqueous cytoplasmic spaces, and proteolipid protein, which spans the bilayers (2). Myelin acts as a transmitter of electric signals known as action potentials, its efficiency being attributed to the low dielectric constant associated with the high lipid content of its closely apposed membranes. Electrical impulses are transmitted along myelinated axons orders of magnitude...

show abstract

Section: Methodsmentioning

confidence: 99%

Synergistic interactions of lipids and myelin basic protein

Doudevski

Wood

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…12 h before cutting, the samples were infused with 2.3 M sucrose for cryoprotection. Sections were cut in a cryo-ultramicrotome at Ϫ 95 Њ C. Immunogold labeling was done according to Griffith (13) as applied to human brain (14). For detection of citrullinated forms of MBP, the sections were labeled with the anticitrulline antibody as primary antibody followed by goat antirabbit IgG complexed to 10-nm gold particles.…”

Section: Methodsmentioning

confidence: 99%

Modifications of myelin basic protein in DM20 transgenic mice are similar to those in myelin basic protein from multiple sclerosis.

Mastronardi

Mak²,

Ackerley³

et al. 1996

J. Clin. Invest.

View full text Add to dashboard Cite

Transgenic mice containing different numbers of transgenes (2-70) of the myelin proteolipid protein DM20 were phenotypically normal up to 3 mo of age, after which the mice containing 70 copies of the transgene spontaneously demyelinated and died at 10-12 mo. Since we demonstrated that demyelination in multiple sclerosis involved specific chemical changes in myelin basic protein (MBP), we investigated the MBP in our transgenic line for similar changes. Both the total amount of MBP in brain and the MBP mRNA levels were unaffected at the different ages. All the isoforms (14-21 kD) of MBP were present, but the microheterogeneity (a posttranslational event) was changed resulting in a higher proportion of the less cationic components reminiscent of the changes in MBP found in multiple sclerosis. An increased amount of the citrullinated form of MBP was found by Western blot analysis. Immunogold labeling of cryosections of brain revealed a greater density of particles with the anticitrulline antibody at 10 mo and that the levels of peptidylarginine deiminase (which deiminates protein-bound arginine to citrulline) were increased. This stable transgenic line represents a useful animal model for the human disease multiple sclerosis. ( J. Clin. Invest. 1996. 97:349-358.)

show abstract

“…Thus, when myelins of different densities were isolated from normal human white matter, the more dense, less compact myelin showed an increased amount of C-8 and a relative deficiency of C-I (18), suggesting that the extent of myelin compaction was determined by the relative proportion of C-1. Since C-8 is the only MBP which contains citrulline, immunogold localization of C-8 in cryosections of human brain biopsies with a citrulline specific antibody, localized this particular charge isomer to the intraperiod line of myelin whereas antibody to the other charge isomers localized MBP to the major dense line (19).…”

Section: Introductionmentioning

confidence: 99%

Myelin in multiple sclerosis is developmentally immature.

Moscarello

Wood²,

Ackerley³

et al. 1994

J. Clin. Invest.

303

275

View full text Add to dashboard Cite

The etiology of multiple sclerosis (MS) is considered to involve genetic, environmental, infective, and immunological factors which affect the integrity of a normally assembled myelin sheath, either directly or indirectly resulting in demyelination. In a correlative study involving protein chemical, mass spectrometric, and electron microscopic techniques we have determined that myelin obtained from victims of MS is arrested at the level of the first growth spurt (within the first 6 yr of life) and is therefore developmentally immature. The data supporting this conclusion include (a) the pattern of microheterogeneity of myelin basic protein (MBP); (b) the NH2-terminal acylation of the least cationic component of MBP ("C-8"); (c) the phase transition temperature (TJ) of myelin isolated from victims of MS correlated with the increased proportion of the least cationic component of MBP; and (d) immunogold electron microscopy using an antibody specific for "C-8" showed that the distribution of gold particles in a 2-yr-old infant was similar to the distribution found in a victim of MS. We postulate that this developmentally immature myelin is more susceptible to degradation by one or a combination of factors mentioned above, providing the initial antigenic material to the immune system. (J. Clin. Invest 1994.94:146-154.)

show abstract

Localization of basic proteins in human myelin

Cited by 38 publications

References 28 publications

Synergistic interactions of lipids and myelin basic protein

Synergistic interactions of lipids and myelin basic protein

Modifications of myelin basic protein in DM20 transgenic mice are similar to those in myelin basic protein from multiple sclerosis.

Myelin in multiple sclerosis is developmentally immature.

Contact Info

Product

Resources

About