title: Drosophila Lipophorin Receptors Recruit the Lipoprotein LTP to the Plasma Membrane to Mediate Lipid Uptake.
abstract: Lipophorin, the main Drosophila lipoprotein, circulates in the hemolymph transporting lipids between organs following routes that must adapt to changing physiological requirements. Lipophorin receptors expressed in developmentally dynamic patterns in tissues such as imaginal discs, oenocytes and ovaries control the timing and tissular distribution of lipid uptake. Using an affinity purification strategy, we identified a novel ligand for the lipophorin receptors, the circulating lipoprotein Lipid Transfer Particle (LTP). We show that specific isoforms of the lipophorin receptors mediate the extracellular accumulation of LTP in imaginal discs and ovaries. The interaction requires the LA-1 module in the lipophorin receptors and is strengthened by a contiguous region of 16 conserved amino acids. Lipophorin receptor variants that do not interact with LTP cannot mediate lipid uptake, revealing an essential role of LTP in the process. In addition, we show that lipophorin associates with the lipophorin receptors and with the extracellular matrix through weak interactions. However, during lipophorin receptor-mediated lipid uptake, LTP is required for a transient stabilization of lipophorin in the basolateral plasma membrane of imaginal disc cells. Together, our data suggests a molecular mechanism by which the lipophorin receptors tether LTP to the plasma membrane in lipid acceptor tissues. LTP would interact with lipophorin particles adsorbed to the extracellular matrix and with the plasma membrane, catalyzing the exchange of lipids between them.
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CSIC-UPO-JA), Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: Míriam
authors.initials: M
authors.lastname: Rodríguez-Vázquez
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CSIC-UPO-JA), Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Vaquero
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CSIC-UPO-JA), Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Parra-Peralbo
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CSIC-UPO-JA), Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: John E
authors.initials: JE
authors.lastname: Mejía-Morales
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CSIC-UPO-JA), Universidad Pablo de Olavide, Sevilla, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Culi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005260:Female; D006458:Hemolymph / Q000378:metabolism; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood / Q000235:genetics; D010053:Ovary / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism
chemical_list: D001053:Apolipoproteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D008074:Lipoproteins; C558442:Lpr1 protein, Drosophila; C558443:Lpr2 protein, Drosophila; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; C000607219:apoLTP protein, Drosophila; C032830:lipophorin