Lipid droplet biology and evolution illuminated by the characterization of a novel perilipin in teleost fish

Abstract

Perilipin (PLIN) proteins constitute an ancient family important in lipid droplet (LD) formation and triglyceride metabolism. We identified an additional PLIN clade (plin6) that is unique to teleosts and can be traced to the two whole genome duplications that occurred early in vertebrate evolution. Plin6 is highly expressed in skin xanthophores, which mediate red/yellow pigmentation and trafficking, but not in tissues associated with lipid metabolism. Biochemical and immunochemical analyses demonstrate that zebrafish Plin6 protein targets the surface of pigment-containing carotenoid droplets (CD). Protein kinase A (PKA) activation, which mediates CD dispersion in xanthophores, phosphorylates Plin6 on conserved residues. Knockout of plin6 in zebrafish severely impairs the ability of CD to concentrate carotenoids and prevents tight clustering of CD within carotenoid bodies. Ultrastructural and functional analyses indicate that LD and CD are homologous structures, and that Plin6 was functionalized early in vertebrate evolution for concentrating and trafficking pigment.DOI: http://dx.doi.org/10.7554/eLife.21771.001

The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis

“…The increment of gene numbers followed by episodes of subfunctionalizations, neofunctionalizations, and gene loss, have all impacted vertebrate physiology, and, in the context of this review, the number and function of genes encoding the perilipins. A fascinating recent theoretical model for the molecular evolution of this gene family is based on the analysis of phylogenetic and conserved synteny (3); this analysis examines the conservation of segments of chromosomes containing multiple genes among closely related organisms. These regions of chromosomes are more highly conserved among evolutionarily related species than they are among distant ancestors.…”

“…Further, the model suggests that a second genome duplication event led to the divergence of perilipin 1 from perilipin 6 and separately, the divergence of perilipin 2 from an ancestral gene that eventually gave rise to perilipin 3, and then perilipins 4 and 5 during tetrapod evolution. Although mammals express perilipins 1 through 5, birds and reptiles express only perilipins 1, 2, 3, and a 5-like gene, and fish express only perilipins 1, 2, 3, and 6 (3). The more recent gene duplication and divergence of the sequences of perilipins 4 and 5 suggests that these perilipins gained specialized functions during the evolution of mammals.…”

“…Only mammals express perilipins 1, 2, 3, 4, and 5. This model was proposed by Granneman, et al (3), and this figure is derived from Figure 1-figure supplement 2 of that paper. Lines in the model are not to scale and do not represent evolutionary timeframes.…”

“…The major isoform of perilipin 1 (perilipin 1A), and perilipins 2 and 5 preferentially associate with lipid droplets enriched in triacylglycerols, whereas shorter isoforms of perilipin 1 (perilipins 1C and 1D) and perilipin 4 preferentially associate with lipid droplets enriched in cholesterol esters (2). Interestingly, perilipin 6, expressed only in teleost fish, associates with lipid droplets containing carotenoid pigments in skin xanthophores (3); in contrast, retinoid containing lipid droplets of mammalian hepatic stellate cells and retinal pigment epithelial cells are coated with perilipins 2 and 3 (4,5). …”

The New Face of the Lipid Droplet: Lipid Droplet Proteins

“…Currently, there are five PLINs (PLIN1–5) known in mammals, and several homologous proteins, based on structural and sequence similarities, in other organisms, such as lipid storage droplets surface‐binding protein 1 (LSD1/PLIN1) and LSD2/PLIN2 in Drosophila . Recently, the sixth PLIN protein, PLIN6, was discovered in zebrafish . Because of their fidelity to the LD, the PLINs, especially PLIN1 and PLIN2, are considered LD marker proteins.…”