title: Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction.
abstract: Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction (P = 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation (P = 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest.
authors: Brock University, Department of Kinesiology, Centre for Bone and Muscle Health, St. Catharines, Canada. rm09aa@brocku.ca
authors: Rebecca E K
authors: RE
authors: MacPherson
authors: Sofhia V
authors: SV
authors: Ramos
authors: Rene
authors: R
authors: Vandenboom
authors: Brian D
authors: BD
authors: Roy
authors: Sandra J
authors: SJ
authors: Peters
mesh_terms: D000217:Acyltransferases; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D004558:Electric Stimulation; D004591:Electrophoresis, Polyacrylamide Gel; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D000070780:Perilipin-2; D000070796:Perilipin-3; D000070797:Perilipin-5; D051381:Rats; D020318:Rats, Long-Evans; D012146:Rest / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C520594:Abhd5 protein, rat; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C544353:PLIN5 protein, rat; D000070780:Perilipin-2; D000070796:Perilipin-3; D000070797:Perilipin-5; C000602984:Plin2 protein, rat; C570203:Plin3 protein, rat; D033921:Vesicular Transport Proteins; D000217:Acyltransferases; D008049:Lipase; C571275:PNPLA2 protein, rat