Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation.
Akey step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin-null animals have an elevated basal rate of lipolysis compared with adipocytes from wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the beta-adrenergic receptor-adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in perilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have also reconstructed the HSL translocation reaction in the nonadipocyte Chinese hamster ovary cell line by introduction of GFP-tagged HSL with and without perilipin A. On activation of protein kinase A, HSL-GFP translocates to lipid droplets only in cells that express fully phosphorylatable perilipin A, confirming that perilipin is required to elicit the HSL translocation reaction. Moreover, in Chinese hamster ovary cells that express both HSL and perilipin A, these two proteins cooperate to produce a more rapidly accelerated lipolysis than do cells that express either of these proteins alone, indicating that lipolysis is a concerted reaction mediated by both protein kinase A-phosphorylated HSL and perilipin A.
Sztalryd
Carole
C
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-2715, USA.
Xu
Guoheng
G
Dorward
Heidi
H
Tansey
John T
JT
Contreras
Juan A
JA
Kimmel
Alan R
AR
Londos
Constantine
C
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000502:physiology; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis / Q000235:genetics*; D051379:Mice; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D010766:Phosphorylation; D021381:Protein Transport / Q000235:genetics; D011993:Recombinant Fusion Proteins; D002787:Sterol Esterase / Q000378:metabolism*
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase