The major myelin-resident protein PLP is transported to myelin membranes via a transcytotic mechanism: involvement of sulfatide

Wia Baron*, Hande Ozgen, Bert Klunder, Jenny C de Jonge, Anita Nomden, Annechien Plat, Elisabeth Trifilieff, Hans de Vries, Dick Hoekstra

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Myelin membranes are sheet-like extensions of oligodendrocytes that can be considered as membrane domains distinct from the cell's plasma membrane. Consistent with the polarized nature of oligodendrocytes we demonstrate that transcytotic transport of the major myelin-resident protein, PLP, is a key element in the mechanism of myelin assembly. Upon biosynthesis, PLP traffics to myelin membranes via syntaxin 3-mediated docking at the apical-like cell body plasma membrane, which is followed by subsequent internalization and transport to the basolateral-like myelin sheet. Pulse chase experiments, in conjunction with surface biotinylation and organelle fractionation, reveal that following biosynthesis, PLP is transported to the cell body surface in TX-100-resistant microdomains. At the plasma membrane, PLP transiently resides within these microdomains, and its lateral dissipation is followed by segregation into CHAPS-resistant domains, internalization and subsequent transport towards the myelin membrane. Sulfatide triggers PLP's reallocation from TX-100- into CHAPS-resistant membrane domains, while inhibition of sulfatide biosynthesis inhibits transcytotic PLP transport. Taken together, we propose a model in which PLP transport to the myelin membrane proceeds via a transcytotic mechanism, mediated by sulfatide, and characterized by a conformational alteration and a dynamic, i.e., transient partitioning of PLP into distinct membrane microdomains, involved in biosynthetic and transcytotic transport.

Original languageEnglish
Pages (from-to)288-302
Number of pages15
JournalMolecular and Cellular Biology
Volume35
Issue number1
DOIs
Publication statusPublished - Jan-2015

Keywords

  • CENTRAL-NERVOUS-SYSTEM
  • PELIZAEUS-MERZBACHER-DISEASE
  • CANINE KIDNEY-CELLS
  • PROTEOLIPID PROTEIN
  • PLASMA-MEMBRANE
  • BASIC-PROTEIN
  • OLIGODENDROCYTE DIFFERENTIATION
  • MONOCLONAL-ANTIBODIES
  • POLARITY DEVELOPMENT
  • MULTIPLE-SCLEROSIS

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