title: The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex.
abstract: Myelin comprises a compactly stacked massive surface area of protein-poor thick membrane that insulates axons to allow fast signal propagation. Increasing levels of the myelin protein plasmolipin (PLLP) were correlated with post-natal myelination; however, its function is unknown. Here, the intracellular localization and dynamics of PLLP were characterized in primary glial and cultured cells using fluorescently labeled PLLP and antibodies against PLLP. PLLP localized to and recycled between the plasma membrane and the Golgi complex. In the Golgi complex, PLLP forms oligomers based on fluorescence resonance energy transfer (FRET) analyses. PLLP oligomers blocked Golgi to plasma membrane transport of the secretory protein vesicular stomatitis virus G protein (VSVG), but not of a VSVG mutant with an elongated transmembrane domain. Laurdan staining analysis showed that this block is associated with PLLP-induced proliferation of liquid-ordered membranes. These findings show the capacity of PLLP to assemble potential myelin membrane precursor domains at the Golgi complex through its oligomerization and ability to attract liquid-ordered lipids. These data support a model in which PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex.
authors.affiliation: Department of Pathology, Sackler School of Medicine, Tel-Aviv 69978, Israel.
authors.forename: Yakey
authors.initials: Y
authors.lastname: Yaffe
authors.affiliation: Department of Pathology, Sackler School of Medicine, Tel-Aviv 69978, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Hugger
authors.affiliation: Department of Pathology, Sackler School of Medicine, Tel-Aviv 69978, Israel.
authors.forename: Inbar Nevo
authors.initials: IN
authors.lastname: Yassaf
authors.affiliation: Department of Pathology, Sackler School of Medicine, Tel-Aviv 69978, Israel.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Shepshelovitch
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv 69978, Israel.
authors.forename: Ella H
authors.initials: EH
authors.lastname: Sklan
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel-Aviv 69978, Israel.
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Elkabetz
authors.affiliation: Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Adva
authors.initials: A
authors.lastname: Yeheskel
authors.affiliation: Bioinformatics Unit, G.S.W. Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: EMBL Australia Node in Single Molecule Science, School of Medical Sciences and ARC Centre of Excellence in Advanced Molecular Imaging, Centre for Vascular Research University of New South Wales, Sydney, Australia 2033.
authors.forename: Carola
authors.initials: C
authors.lastname: Benzing
authors.affiliation: Biomedical Imaging Facility, University of New South Wales, Sydney, Australia 2033.
authors.forename: Alexander
authors.initials: A
authors.lastname: Macmillan
authors.affiliation: EMBL Australia Node in Single Molecule Science, School of Medical Sciences and ARC Centre of Excellence in Advanced Molecular Imaging, Centre for Vascular Research University of New South Wales, Sydney, Australia 2033.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel 76100.
authors.forename: Yael
authors.initials: Y
authors.lastname: Eshed-Eisenbach
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel 76100.
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.affiliation: Department of Pathology, Sackler School of Medicine, Tel-Aviv 69978, Israel koty@post.tau.ac.il.
authors.forename: Koret
authors.initials: K
authors.lastname: Hirschberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D004285:Dogs; D004705:Endocytosis; D006056:Golgi Apparatus / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; C048897:PLLP protein, human; D011510:Proteolipids
keywords: Golgi complex; Myelin; Plasmolipin