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.

Oral transfer of chemical cues, growth proteins and hormones in social insects

“…Although the mechanisms of JH uptake by tissues are still incompletely understood (Parra-Peralbo and Culi, 2011; Rodríguez-Vázquez et al, 2015; Engelmann and Mala, 2000; Suzuki et al, 2011), the TF proteins apolipophorin, hexamerin, JH-binding protein and vitellogenin have all been implicated in JH binding and transport between hemolymph and tissues (Goodman and Granger, 2009; Rodríguez-Vázquez et al, 2015; Engelmann and Mala, 2000; Suzuki et al, 2011; Amsalem et al, 2014), and these factors may be responsible for transporting JH into the foregut. Unfortunately, even in Drosophila mechanisms of JH uptake by tissues are still unclear (Rodríguez-Vázquez et al, 2015; Engelmann and Mala, 2000; Suzuki et al, 2011; Parra-Peralbo and Culi, 2011). Extracellular miRNAs are secreted and transported through a variety of pathways, but the functional relevance of such molecules is still controversial (Sarkies and Miska, 2013; Turchinovich et al, 2016; Masood et al, 2016; Søvik et al, 2015; Rayner and Hennessy, 2013).…”

Triacylglycerol Metabolism in Drosophila melanogaster

“…After its secretion by the fat body or cardiac muscle, Lpp is recruited to the midgut, where it is loaded with diet-derived DAG and sterols that are then redistributed to other tissues. As a consequence, RNAimediated interference of the hemolymph Lpp system manifests in a massive accumulation of LDs in the midgut of feeding third-instar larvae (Panáková et al 2005;Palm et al 2012), and in a concomitant depletion of lipid in other tissues such as the brain or imaginal discs (Palm et al 2012;Rodríguez-Vázquez et al 2015). Biochemical studies in non-Drosophila insects indicate that lipid delivery to tissues via Lpp occurs without concomitant degradation of ApoLI/II proteins, suggesting that Lpp acts as a reusable lipid shuttle (Downer and Chino 1985;Arrese et al 2001).…”

“…Genetic depletion of LTP in Drosophila third-instar larvae compromises Lpp recruitment to the midgut and its loading with DAG, resulting in ectopic LD accumulation in the midgut epithelium (Palm et al 2012). LTP activity has also been implicated in lipid transfer from lipid-loaded Lpp to the ovaries and wing discs (Rodríguez-Vázquez et al 2015).…”

“…This phenotype is only partially tissue-autonomous as germline-specific deficiency causes reduced oocyte storage lipid content, but not midoogenesis degeneration (Parra-Peralbo and Culi 2011). In addition, LpR2 has also been assigned a predominant role in lipid uptake into larval oenocytes upon fasting, whereas both LpR1 and LpR2 act redundantly in mediating lipid acquisition of the wing disc (Parvy et al 2012;Rodríguez-Vázquez et al 2015). Notably, whole-body TAG content and mobilization were unaffected by genetic deficiency of LpR1 and LpR2, suggesting that the major routes of lipid transport are not grossly impaired.…”

Clathrin‐dependent endocytosis predominantly mediates protein absorption by fat body from the hemolymph in Bombyx mori

“…In addition, except for the dominant hexamerins, there were ∼40 types of proteins at low quantities in both hemolymph and fat body by MS analysis. Among these proteins, apolipophorins, transferrin, fibrinogen and low molecular 30 kDa lipoprotein were previously reported to be transported into cells more or less via clathrin‐dependent endocytosis mediated by their receptors (Dantuma et al ., ; Hung et al ., ; Fruttero et al ., ; Rodríguez‐Vezquez et al ., ). Typically, phenoloxidases, which are presumed to be secreted and released from the fat body, were also identified in both hemolymph and fat body; however, their precise regulatory mechanism is unclear (Chen et al ., ; Kumar et al ., ; Wang et al ., ).…”