A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover.
HECT (homologous to the E6AP C terminus) ubiquitin ligases have diverse functions in eukaryotic cells. In screens for proteins that bind to the HECT ubiquitin ligase WWP1, we identified Spartin, which is also known as SPG20. This protein is truncated in a neurological disease, Troyer syndrome. In this study, we show that SPG20 associates with the surface of lipid droplets (LDs) and can regulate their size and number. SPG20 binds to another LD protein, TIP47, and both proteins compete with an additional LD protein, adipophilin/adipocyte differentiation-related protein, for occupancy of LDs. The mutant SPG20 present in Troyer syndrome does not possess these activities. Depletion of SPG20 using RNA interference increases the number and size of LDs when cells are fed with oleic acid. Binding of WWP1 to SPG20 and the consequent ubiquitin transfer remove SPG20 from LDs and reduce the levels of coexpressed SPG20. These experiments suggest functions for ubiquitin ligases and SPG20 in the regulation of LD turnover and potential pathological mechanisms in Troyer syndrome.
Eastman
Scott W
SW
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Yassaee
Mina
M
Bieniasz
Paul D
PD
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D000070780:Perilipin-2; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism*; D013577:Syndrome; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; C038196:PLIN3 protein, human; D000070780:Perilipin-2; D000070796:Perilipin-3; D011257:Pregnancy Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C464787:SPART protein, human; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; D019301:Oleic Acid; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases