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Ectopic lipid accumulation in lipid droplets (LD) has been linked to many metabolic diseases. In this study, DHS-3::GFP was used as a LD marker in  C .  elegans  and a forward genetic screen was carried out to find novel LD regulators. There were 140 mutant alleles identified which were divided into four phenotypic categories: enlarged, aggregated, aggregated and small, and decreased. After genetic mapping, mutations in three known LD regulatory genes ( maoc-1 ,  dhs-28 ,  daf-22 ) and a peroxisome-related gene ( acox-3 ) were found to enlarge LDs, demonstrating the reliability of using DHS-3 as a living marker. In the screen, the cytoskeleton protein  C27H5 . 2  was found to be involved in LD aggregation, as was the LD resident/structure-like protein, MDT-28/PLIN-1. Using yeast two-hybrid screening and pull-down assays, MDT-28/PLIN-1 was found to bind to DLC-1 (dynein light chain). Fluorescence imaging confirmed that MDT-28/PLIN-1 mediated the interaction between DHS-3 labeled LDs and DLC-1 labeled microtubules. Furthermore, MDT-28/PLIN-1 was directly bound to DLC-1 through its amino acids 1–210 and 275–415. Taken together, our results suggest that MDT-28/PLIN-1 is involved in the regulation of LD distribution through its interaction with microtubule-related proteins.

MDT-28/PLIN-1 mediates lipid droplet-microtubule interaction via DLC-1 in Caenorhabditis elegans