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Conserved C‐terminal arginines are crucial for targeting PNPLA5/GS2‐like triglyceride lipase to lipid droplets
Author(s) -
Murugesan Sricharan,
Goldberg Elysa B.,
Brown William J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.643.11
Subject(s) - lipase , biochemistry , adipose triglyceride lipase , arginine , lipid droplet , alanine , conserved sequence , lipid metabolism , triglyceride lipase , biology , amino acid , chemistry , enzyme , peptide sequence , gene
Lipid droplets (LDs) are highly conserved storage depots for triglycerides (TGs) and cholesterol esters. The Patatin‐like Phospholipase Domain containing protein A (PNPLA1‐9) family of neutral lipases play key roles in the hydrolysis of stored TGs and in the regulation of LD metabolism. Previous work in our lab has uncovered a conserved charge‐dependent LD targeting motif (LTM) in the C‐terminal third of human PNPLA5 and Brummer Lipase (BL), the Drosophila homolog of human Adipose Triglyceride Lipase (PNPLA2/ATGL). The LTM of PNPLA5 is a conserved basic patch containing three arginine residues, two of which, if mutated to alanines abolish LD association. Here we report that each of these arginine residues is crucial for targeting PNPLA5 to LDs. Transient transfection of full‐length PNPLA5 containing all possible arginine to alanine changes revealed that altering any one of the arginines abolished LD association in vivo. However, mutations of similar putative basic patches in human PNPLA2/ATGL revealed only mild mislocalization. These results show that although conserved arginines in basic patches of PNPLA5 and BL identify a conserved LTM, not all family members are recruited to LDs in an identical manner. This correlates with evidence that PNPLA family members serve overlapping, but not identical, roles in TG homeostasis. This work supported by Hatch Project NYC‐165415 and NIH grant DK51596 to WJB.