Insulin and oleate promote translocation of inosine-5 &#39; monophosphate dehydrogenase to lipid bodies

Whitehead, JP; Simpson, F; Hill, MM; Thomas, EC; Connolly, LM; Collart, F; Simpson, RJ; James, DE

Insulin and oleate promote translocation of inosine-5 ' monophosphate dehydrogenase to lipid bodies

Author(s): Whitehead, JP; Simpson, F; Hill, MM; Thomas, EC; Connolly, LM; Collart, F; Simpson, RJ; James, DE;
Details: Publication Year 2004-10,Volume 5,Issue #10,Page 739-749
Journal Title: TRAFFIC
Publication Type: Journal Article
Abstract: In the present study we identify inosine-5' monophosphate dehydrogenase (IMPDH), a key enzyme in de novo guanine nucleotide biosynthesis, as a novel lipid body-associated protein. To identify new targets of insulin we performed a comprehensive 2-DE analysis of P-32-labelled proteins isolated from 3T3-L1 adipocytes (Hill et al. J Biol Chem 2000; 275: 24313-24320). IMPDH was identified by liquid chromatography/tandem mass spectrometry as a protein which was phosphorylated in a phosphatidylinositol (PI) 3-kinase-dependent manner upon insulin treatment. Although insulin had no significant effect on IMPDH activity, we observed translocation of IMPDH to lipid bodies following insulin treatment. Induction of lipid body formation with oleic acid promoted dramatic redistribution of IMPDH to lipid bodies, which appeared to be in contact with the endoplasmic reticulum, the site of lipid body synthesis and recycling. Inhibition of PI 3-kinase blocked insulin- and oleate-induced translocation of IMPDH and reduced oleate-induced lipid accumulation. However, we found no evidence of oleate-induced IMPDH phosphorylation, suggesting phosphorylation and translocation may not be coupled events. These data support a role for IMPDH in the dynamic regulation of lipid bodies and fatty acid metabolism and regulation of its activity by subcellular redistribution in response to extracellular factors that modify lipid metabolism.
Publisher: BLACKWELL MUNKSGAARD
Keywords: DIFFERENTIATION-RELATED PROTEIN; DOMINANT RETINITIS-PIGMENTOSA; STIMULATED GLUCOSE-TRANSPORT; IMP DEHYDROGENASE; 5'-MONOPHOSPHATE DEHYDROGENASE; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR SUBSTRATE-1; 3T3-L1 ADIPOCYTES; STORAGE DROPLETS; NEGATIVE MUTANT
Publisher's Version: https://doi.org/10.1111/j.1600-0854.2004.00217.x
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Creation Date: 2004-10-01 12:00:00