title: The major myelin-resident protein PLP is transported to myelin membranes via a transcytotic mechanism: involvement of sulfatide.
abstract: Myelin membranes are sheet-like extensions of oligodendrocytes that can be considered 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 proteolipid 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-surface-like cell body plasma membrane, which is followed by subsequent internalization and transport to the basolateral-surface-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 Triton X-100 (TX-100)-resistant microdomains. At the plasma membrane, PLP transiently resides within these microdomains and its lateral dissipation is followed by segregation into 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS)-resistant domains, internalization, and subsequent transport toward 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. Taking these findings 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 dynamic, i.e., transient, partitioning of PLP into distinct membrane microdomains involved in biosynthetic and transcytotic transport.
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands w.baron@umcg.nl.
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hande
authors.initials: H
authors.lastname: Ozgen
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Klunder
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: de Jonge
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Nomden
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annechien
authors.initials: A
authors.lastname: Plat
authors.affiliation: UMR_S U1119 INSERM/Université de Strasbourg, Faculté de Médecine, Strasbourg, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Trifilieff
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: de Vries
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
mesh_terms: D000818:Animals; D001692:Biological Transport; D019921:Biotinylation; D002462:Cell Membrane / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry; D018991:Myelin Proteolipid Protein / Q000502:physiology*; D009186:Myelin Sheath / Q000737:chemistry*; D017830:Octoxynol / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013433:Sulfoglycosphingolipids / Q000737:chemistry*
chemical_list: D003902:Detergents; D000939:Epitopes; D018991:Myelin Proteolipid Protein; D013433:Sulfoglycosphingolipids; D017830:Octoxynol