Diffraction Studies of Molecular Organization and Membrane Interactions in Myelin

Kirschner, Daniel A.; Ganser, A.; Caspar, D. L. D.

doi:10.1007/978-1-4757-1830-0_2

Cited by 88 publications

(98 citation statements)

References 75 publications

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Section: Introductionmentioning

confidence: 99%

“…During maturation, the membranes become compacted with a close apposition of both the internal and external faces of the membrane. The relative thicknesses of the bilayer, cytoplasmic, and extracellular spaces are 47 A, 30 A, and 30 A, respectively (2,3).Although the myelin sheath is characterized by a relatively high proportion of lipid (70-80%), it is the myelin proteins that provide specificity and perform an important, albeit illdefined role in the maintenance of myelin structure. The predominant proteins are the water-soluble extrinsic myelin basic protein (Mr 18,000), characterized by a high proportion of basic and other polar amino acids (4,5), and the hydrophobic, chloroform/methanol-soluble proteolipid (Mr 30,000) (4, 6).…”

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confidence: 99%

See 1 more Smart Citation

The structure of bovine brain myelin proteolipid and its organization in myelin.

Laursen¹,

Samiullah²,

Lees³

1984

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

124

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A model, based on amino acid sequence data, is proposed for the organization of the myelin proteolipid in myelin membrane. The model has three distinctive features: three trans-membrane segments that traverse the lipid bilayer, two cis-membrane domains that enter and exit the same side of the membrane, and a highly charged segment resembling myelin basic protein on the cytoplasmic side of the membrane. It is proposed that the cis-membrane domain(s) can promote the formation and stabilization of the multilamellar myelin structure by hydrophobic interaction with the apposite bilayer across the extracellular space.In the central nervous system, myelin is formed as an extended, modified oligodendroglial plasma membrane that spirals around the axon to form a multilamellar structure (1). During maturation, the membranes become compacted with a close apposition of both the internal and external faces of the membrane. The relative thicknesses of the bilayer, cytoplasmic, and extracellular spaces are 47 A, 30 A, and 30 A, respectively (2,3).Although the myelin sheath is characterized by a relatively high proportion of lipid (70-80%), it is the myelin proteins that provide specificity and perform an important, albeit illdefined role in the maintenance of myelin structure. The predominant proteins are the water-soluble extrinsic myelin basic protein (Mr 18,000), characterized by a high proportion of basic and other polar amino acids (4,5), and the hydrophobic, chloroform/methanol-soluble proteolipid (Mr 30,000) (4, 6). The basic protein is well-characterized (4, 5); however, the proteolipid has resisted structure elucidation, and only recently has its amino acid sequence been determined (7-9). In this article we propose a model ( Fig. 1) for bovine brain myelin proteolipid, based on amino sequence data and analogy with other proteins, and suggest how the proteolipid may help to stabilize the myelin sheath. RESULTS AND DISCUSSIONGeneral Structural Features. The most notable characteristic of the proteolipid sequence (Fig. 2) is the clustering of hydrophobic amino acids into distinct domains. A plot of amino acid hydropathy (11) (Fig. 3) shows four hydrophobic domains of about 30 amino acids each, which alternate with polar segments containing most of the charged and neutral hydrophilic residues. The polar domains also contain all of the predicted ,B-turns (12), suggesting that these regions are extensively folded. These features suggest a model, such as has been proposed for bacteriorhodopsin (13) and other intrinsic membrane proteins (14), wherein the polypeptide chain passes repeatedly through the lipid bilayer, the hydrophobic regions being embedded in the lipid and the polar domains exposed on the external and internal faces of the membrane (Fig. 1). For purposes of discussion, various domains in the proteolipid are defined in terms of polarity, proposed orientation in the membrane, and sequence homology. Thus, Ti (residues 59-90), T2 (residues 151-177) and T3 (residues 238-267) are hydrophobic trans-membrane se...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

The structure of bovine brain myelin proteolipid and its organization in myelin.

Laursen¹,

Samiullah²,

Lees³

1984

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

124

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“…Myelin is a mem brane with unique characteristics that set it apart from any other membrane. It has a very high lipid:protein ratio (= 75:25) not found in other multilamellar mem branes, e.g., rod outer segment disk membrane ( = 333 50:50) [23] or grana thylakoid membrane ( = 60:40) [24]; suggesting that the high lipid content may not be the prime determinant in membrane apposition [25]. Like wise, the high glycolipid content, though also found in the thylakoid membrane, may not be a critical factor in regulating myelin structure [25].…”

Section: Discussionmentioning

confidence: 99%

Myelin Palingenesis

Arvanitis

Dumas²,

Szuchet³

1992

Dev Neurosci

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Myelin is a membrane with unique characteristics that set it apart from any other membrane. It has a very high lipid:protein ratio (≈ 75:25) not found in other multilamellar membranes; it has a high content of two glycolipids -galactocerebrosides and sulfatides - which account for 26.5% of its lipids. The physiological role of these glycolipids in myelin and/or oligodendrocytes is unknown, but evidence that Abs directed against them interfere with myelination has been presented. Moreover, one of the early events in the process of oligodendrocyte differentiation prior to myelination is the acquisition of galactocerebroside on their surface. In earlier work, we have demonstrated that adhesion of oligodendrocytes to a positively charged substratum signals the commencement of myelinogenesis. Among the events that take place following adhesion are the rapid synthesis of glycolipids. Since over time in culture, oligodendrocytes elaborate multilamellar membranes that contain all the myelin characteristic proteins, we undertook to investigate whether these structures also accumulate myelin characteristic glycolipids. We have used three monoclonal antibodies - two are directed against galactocerebroside, the third one is an antisulfatide - in conjunction with the immunogold method, at the electron microscopic level, to examine the distribution of these glycolipids in the multilammelar structures that accumulate in long-term oligodendrocyte cultures. Our data show that galactocerebrosides and sulfatides are present in the multilamellar structures. Staining is easily demonstrated on the outermost membrane. However, as was the situation with myelin proteins, detection of these glycolipids on the inner lamellae is only achieved at the expense of destroying the ultrastructure. This is so, independent of whether the structures are compact or not. These results also serve to illustrate the distribution of these glycolipids on the surface of oligodendrocytes and their processes.

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“…Myelin is electrically insulating the axons, allowing fast, saltatory nerve impulse conduction. The composition [3,4,5,6,7,8] and structure [9,10] of the myelin sheath are well studied. Myelin is a lipid-rich membrane, composed of 75 -80% anionic and neutral lipids and 20 -25% proteins [8].…”

Section: Introductionmentioning

confidence: 99%

The Influence of the Myelin Basic Protein C8 Mutant on the Dynamics of Myelin Membranes

et al. 2013

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Diffraction Studies of Molecular Organization and Membrane Interactions in Myelin

Cited by 88 publications

References 75 publications

The structure of bovine brain myelin proteolipid and its organization in myelin.

The structure of bovine brain myelin proteolipid and its organization in myelin.

Myelin Palingenesis

The Influence of the Myelin Basic Protein C8 Mutant on the Dynamics of Myelin Membranes

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