Perilipin-related protein regulates lipid metabolism inC. elegans

Abstract

Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. In mutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism.

The lipid droplet: A conserved cellular organelle

“…The LD resident proteins in C . elegans , DHS-3 and MDT-28/PLIN1 (Chughtai et al, 2015 ) behave similarly to target mammalian LDs (Na et al 2015 ). In addition, a Drosophila LD resident protein, LSD1/PLIN1 localizes to LDs in C .…”

The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator ofC. elegansdevelopment

“…This is supported by our findings that F28F8.5 interacts with nematode homologues of MED6 and MED30 (MDT-6, and MDT-30), the close sequence similarity of F28F8.5 to MED28 detected informatically in nematode genomes, a conserved dual nuclear and cytoplasmic expression pattern, and its involvement in a wide range of developmental processes. Thus we suggest F28F8.5 be identified as MDT-28, with the original gene for MDT-28 now recognized as the nematode homologue of perilipin, now named PLIN-1 ( Chughtai et al, 2015 ).…”

“…The relatively low conservation of Mediator complex subunits between eukaryotic phyla ( Poss, Ebmeier & Taatjes, 2013 ; Allen & Taatjes, 2015 ) makes the identification of orthologues in distant species difficult and some suggested orthologues may require re-classification. Our previous work showed that the protein previously identified as “MDT-28” ( M e d ia t or-28) in nematodes ( Bourbon, 2008 ) is instead the nematode homologue of perilipin, a protein regulating lipid metabolism at the level of lipid droplets and is not related to MED28 ( Chughtai et al, 2015 ). Thinking it was unlikely that a MED28 homologue would be absent in nematode genomes, we searched for it using the conserved features of MED28 orthologues from various phyla.…”

Current advances in the functional studies of fatty acids and fatty acid-derived lipids inC. elegans

“…55 Moreover, some lipid droplet-related proteins, such as PLIN-1, MDT-28 and ACS-4, may be used as markers to indicate lipid droplet dynamics. [56][57][58][59] Their work provides spatial information of different biomolecules in individual worms and may be useful for studying lipid localization and lipid-protein interactions.…”