Dataset Information

Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the Myelin Major Dense Line.

ABSTRACT: Compact myelin comprises most of the dry weight of myelin, and its insulative nature is the basis for saltatory conduction of nerve impulses. The major dense line (MDL) is a 3-nm compartment between two cytoplasmic leaflets of stacked myelin membranes, mostly occupied by a myelin basic protein (MBP) phase. MBP is an abundant myelin protein involved in demyelinating diseases, such as multiple sclerosis. The association of MBP with lipid membranes has been studied for decades, but the MBP-driven formation of the MDL remains elusive at the biomolecular level. We employed complementary biophysical methods, including atomic force microscopy, cryo-electron microscopy, and neutron scattering, to investigate the formation of membrane stacks all the way from MBP binding onto a single membrane leaflet to the organisation of a stable MDL. Our results support the formation of an amorphous protein phase of MBP between two membrane bilayers and provide a molecular model for MDL formation during myelination, which is of importance when understanding myelin assembly and demyelinating conditions.

SUBMITTER: Raasakka A

PROVIDER: S-EPMC5504075 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the Myelin Major Dense Line.

Raasakka Arne A Ruskamo Salla S Kowal Julia J Barker Robert R Baumann Anne A Martel Anne A Tuusa Jussi J Myllykoski Matti M Bürck Jochen J Ulrich Anne S AS Stahlberg Henning H Kursula Petri P

Scientific reports 20170710 1

Compact myelin comprises most of the dry weight of myelin, and its insulative nature is the basis for saltatory conduction of nerve impulses. The major dense line (MDL) is a 3-nm compartment between two cytoplasmic leaflets of stacked myelin membranes, mostly occupied by a myelin basic protein (MBP) phase. MBP is an abundant myelin protein involved in demyelinating diseases, such as multiple sclerosis. The association of MBP with lipid membranes has been studied for decades, but the MBP-driven f ...[more]

PMID: 28694532

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Project description:Hypo-osmotic homogenization of the endoneurium from the adult-rat sciatic nerve and subsequent evaluation of the 197 000 g aqueous supernatant by sodium dodecyl sulphate pore-gradient electrophoresis (SDS-p.g.e.) revealed a release of the major glycoprotein (P0) (29 000 Mr) from peripheral nerve myelin. Immunological verification of the presence of this asparagine-linked glycoprotein in the aqueous supernatant was obtained by immune overlay after SDS-p.g.e. and electrophoretic transfer to nitrocellulose using anti-P0 gamma-globulin followed by autoradiographic detection with 125I-protein A. A comparison of successive hypo- and iso-osmotic extractions of the endoneurium revealed that the hypo-osmotic extraction released increasing amounts of P0 into the supernatant fraction, whereas the iso-osmotic treatment revealed lower levels of P0 extracted from the myelin and lesser amounts with each successive extraction. Three successive hypo-osmotic extractions resulted in a 2.0-, 2.9-, and 9.5-fold increase in the amount of P0 released compared with the successive iso-osmotic extractions. Although these results suggest that this major myelin glycoprotein has properties similar to those of extrinsic membrane proteins, temperature-dependent phase-partitioning experiments with Triton X-114 revealed that this glycoprotein is recovered in the detergent-enriched lower phase. These results indicate that this major myelin glycoprotein is an amphipathic integral membrane protein with a distinct hydrophobic domain and yet has solubility characteristics typical of an extrinsic membrane protein. P0 labelled in vitro with [3H]mannose could be immunoprecipitated from the aqueous supernatant with anti-P0 gamma-globulin by centrifugation at 197000g without the addition of second antibody or protein A. Analysis of such an immune precipitate after incorporation in vitro with [14C]acetate to label endoneurial lipids revealed that all major endoneurial lipid classes contained radioactive label, as determined by fluorography after high-performance t.l.c. The mechanism of release of this intrinsic glycoprotein from the myelin membrane, therefore, involves the osmotic-dependent formation of mixed micelles or membrane vesicles with endogenous membrane lipids.

Dataset Information

Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the Myelin Major Dense Line.

Publications

Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the Myelin Major Dense Line.

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