Opposite and redundant roles of the two Drosophila perilipins in lipid mobilization

Abstract

SummaryLipid droplets are the main lipid storage sites in cells. Lipid droplet homeostasis is regulated by the surface accessibility of lipases. Mammalian adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are two key lipases for basal and stimulated lipolysis, respectively. Perilipins, the best known lipid droplet surface proteins, can either recruit lipases or prevent the access of lipases to lipid droplets. Mammals have five perilipin proteins, which often exhibit redundant functions, precluding the analysis of the exact role of individual perilipins in vivo. Drosophila have only two perilipins, PLIN1/LSD-1 and PLIN2/LSD-2. Previous studies revealed that PLIN2 is important for protecting lipid droplets from lipolysis mediated by Brummer (BMM), the Drosophila homolog of ATGL. In this study, we report the functional analysis of PLIN1 and Drosophila HSL. Loss-of-function and overexpression studies reveal that unlike PLIN2, PLIN1 probably facilitates lipid mobilization. HSL is recruited from the cytosol to the surface of lipid droplets under starved conditions and PLIN1 is necessary for the starved induced lipid droplet localization of HSL. Moreover, phenotypic analysis of plin1;plin2 double mutants revealed that PLIN1 and PLIN2 might have redundant functions in protecting lipid droplets from lipolysis. Therefore, the two Drosophila perilipins have both opposite and redundant roles. Domain swapping and deletion analyses indicate that the C-terminal region of PLIN1 confers functional specificity to PLIN1. Our study highlights the complex roles of Drosophila perilipin proteins and the evolutionarily conserved regulation of HSL translocation by perilipins.

Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

“…There are small lipid droplets (1-4 mm) that express the markers Lsd-2 and Lsd-1 and larger lipid droplets (.4 mm) that express only Lsd1 (Bi et al 2012). Expression of UAS-Lsd2-GFP in the fat body specifically labeled the spectrin-dependent population of small cortical lipid droplets described above (Figure 3, A-C).…”

“…These lipid droplets were previously recognized by their small size and distinct protein composition relative to other lipid droplets in the same cells (Bi et al 2012). The physiological properties of these lipid droplets can now be considered in light of their intimate association with the plasma membrane via spectrin.…”

Lipid droplet-based storage fat metabolism in Drosophila

“…Dm HSL is a member of the embryonic LD proteome ( 13 ), consistent with a putative function in LDbased lipid metabolism. In fat body cells of fed larvae, however, tagged Dm HSL fusion protein does not localize to LDs ( 57 ). However, starvation induces accumulation of this fusion protein on the surface of LDs of larval fat body cells ( 57 ).…”

“…In fat body cells of fed larvae, however, tagged Dm HSL fusion protein does not localize to LDs ( 57 ). However, starvation induces accumulation of this fusion protein on the surface of LDs of larval fat body cells ( 57 ). Starvation induces acute TG lipolysis in Drosophila , which is blunted in AKHR mutant fat body cells ( 44 ).…”

A comparative perspective on lipid storage in animals

“…Furthermore, insects express two PAT family proteins, lipid storage droplet-1 (Lsd-1) and Lsd-2. Although these proteins are localized on the LD surface, they have both opposing and redundant functions (Bi et al, 2012). Lsd-1 modulates the accessibility of lipases, such as Drosophila hormone sensitive lipase (Hsl), to the LD and stabilizes the structure of the LD (Arrese et al, 2008;Beller et al, 2010).…”