title: GLTP mediated non-vesicular GM1 transport between native membranes.
abstract: Lipid transfer proteins (LTPs) are emerging as key players in lipid homeostasis by mediating non-vesicular transport steps between two membrane surfaces. Little is known about the driving force that governs the direction of transport in cells. Using the soluble LTP glycolipid transfer protein (GLTP), we examined GM1 (monosialotetrahexosyl-ganglioside) transfer to native membrane surfaces. With artificial GM1 donor liposomes, GLTP can be used to increase glycolipid levels over natural levels in either side of the membrane leaflet, i.e., external or cytosolic. In a system with native donor- and acceptor-membranes, we find that GLTP balances highly variable GM1 concentrations in a population of membranes from one cell type, and in addition, transfers lipids between membranes from different cell types. Glycolipid transport is highly efficient, independent of cofactors, solely driven by the chemical potential of GM1 and not discriminating between the extra- and intracellular membrane leaflet. We conclude that GLTP mediated non-vesicular lipid trafficking between native membranes is driven by simple thermodynamic principles and that for intracellular transport less than 1 µM GLTP would be required in the cytosol. Furthermore, the data demonstrates the suitability of GLTP as a tool for artificially increasing glycolipid levels in cellular membranes.
authors.affiliation: Department of Membrane Biochemistry, LIMES (Life and Medical Sciences) Institute, University of Bonn, Bonn, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Lauria
authors.forename: Jan
authors.initials: J
authors.lastname: van Üüm
authors.forename: Esmina
authors.initials: E
authors.lastname: Mjumjunov-Crncevic
authors.forename: David
authors.initials: D
authors.lastname: Walrafen
authors.forename: Luis
authors.initials: L
authors.lastname: Spitta
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiele
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lang
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D019169:Jurkat Cells; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D009154:Mutation
chemical_list: D002352:Carrier Proteins; C511922:GLTP protein, human; D008051:Lipid Bilayers; D008081:Liposomes; D005677:G(M1) Ganglioside
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