Myelin Membrane Assembly Is Driven by a Phase Transition of Myelin Basic Proteins Into a Cohesive Protein Meshwork

Shweta Aggarwal, Nicolas Snaidero, Gesa Paehler, Steffen Frey, Paula Sanchez, Markus Zweckstetter, Andreas Janshoff, Anja Schneider, Marie-Theres Weil, Iwan A. T. Schaap, Dirk Goerlich, Mikael Simons

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Abstract

Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system.

Original languageEnglish
Article numbere1001577
Number of pages14
JournalPLoS Biology
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • ADENOASSOCIATED VIRUS
  • NERVOUS-SYSTEM
  • SURFACE-CHARGE
  • RNA GRANULES
  • P GRANULES
  • DISEASE
  • DOMAINS
  • CELLS
  • DIFFERENTIATION
  • EXPRESSION

Cite this

Aggarwal, S., Snaidero, N., Paehler, G., Frey, S., Sanchez, P., Zweckstetter, M., Janshoff, A., Schneider, A., Weil, M-T., Schaap, I. A. T., Goerlich, D., & Simons, M. (2013). Myelin Membrane Assembly Is Driven by a Phase Transition of Myelin Basic Proteins Into a Cohesive Protein Meshwork. PLoS Biology, 11(6), [e1001577]. https://doi.org/10.1371/journal.pbio.1001577