title: The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix.
abstract: In the central nervous system, lipid-protein interactions are pivotal for myelin maintenance, as these interactions regulate protein transport to the myelin membrane as well as the molecular organization within the sheath. To improve our understanding of the fundamental properties of myelin, we focused here on the lateral membrane organization and dynamics of peripheral membrane protein 18.5-kDa myelin basic protein (MBP) and transmembrane protein proteolipid protein (PLP) as a function of the typical myelin lipids galactosylceramide (GalC), and sulfatide, and exogenous factors such as the extracellular matrix proteins laminin-2 and fibronectin, employing an oligodendrocyte cell line, selectively expressing the desired galactolipids. The dynamics of MBP were monitored by z-scan point fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), while PLP dynamics in living cells were investigated by circular scanning FCS. The data revealed that on an inert substrate the diffusion rate of 18.5-kDa MBP increased in GalC-expressing cells, while the diffusion coefficient of PLP was decreased in sulfatide-containing cells. Similarly, when cells were grown on myelination-promoting laminin-2, the lateral diffusion coefficient of PLP was decreased in sulfatide-containing cells. In contrast, PLP's diffusion rate increased substantially when these cells were grown on myelination-inhibiting fibronectin. Additional biochemical analyses revealed that the observed differences in lateral diffusion coefficients of both proteins can be explained by differences in their biophysical, i.e., galactolipid environment, specifically with regard to their association with lipid rafts. Given the persistence of pathological fibronectin aggregates in multiple sclerosis lesions, this fundamental insight into the nature and dynamics of lipid-protein interactions will be instrumental in developing myelin regenerative strategies.
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: Physical Chemistry, Department of Chemistry, Munich Center for Integrated Protein Science (CiPSM) and Center for Nanoscience (CeNS), Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Schrimpf
authors.affiliation: Physical Chemistry, Department of Chemistry, Munich Center for Integrated Protein Science (CiPSM) and Center for Nanoscience (CeNS), Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Jelle
authors.initials: J
authors.lastname: Hendrix
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: Physical Chemistry, Department of Chemistry, Munich Center for Integrated Protein Science (CiPSM) and Center for Nanoscience (CeNS), Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Don C
authors.initials: DC
authors.lastname: Lamb
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
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Kahya
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
mesh_terms: D000818:Animals; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000502:physiology; D038983:Galactolipids / Q000378:metabolism*; D007797:Laminin / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
chemical_list: D005353:Fibronectins; D038983:Galactolipids; D007797:Laminin; C436006:Mbp protein, rat; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; C489071:Plp1 protein, rat