Identification of mouse Prp19p as a lipid droplet-associated protein and its possible involvement in the biogenesis of lipid droplets.
Prp19p is an integral component of the heteromeric protein complex (the NineTeen complex) in the nucleus, and it is essential for the structural integrity of NineTeen complex and its subsequent activation of the spliceosome. We identified Prp19p, which has never been reported in relation to any function outside of the nucleus, as a member of proteins associated with lipid droplets. Down-regulation of Prp19p expression with RNA interference in 3T3-L1 cells repressed lipid droplet formation with the reduction in the level of expression of perilipin and S3-12. The levels of expression of SCD1 (stearoyl-CoA desaturase-1), DGAT-1 (acyl-CoA diacylglycerol acyltransferase-1), and glycerol-3-phosphate acyltransferase were also reduced in Prp19p down-regulated cells, and a significant decrease in triglycerides was observed. Unlike perilipin, which is one of the most extensively studied lipid droplet-associated proteins, Prp19p is not essential for cAMP- and hormone-sensitive lipase-dependent lipolysis pathways, even though Prp19p is a component of the lipid droplet phospholipid monolayer, and down-regulation of Prp19p represses fat accretion significantly. These results suggest that Prp19p or Prp19-interacting proteins during lipid droplet biogenesis in adipocytes may be considered as another class of potential targets for attacking obesity and obesity-related problems.
Cho
Si Young
SY
R & D Center, AmorePacific Corp., 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-729, Korea.
Shin
Eui Seok
ES
Park
Pil Joon
PJ
Shin
Dong Wook
DW
Chang
Hui Kyoung
HK
Kim
Daegun
D
Lee
Hyoung Ho
HH
Lee
Jeong Ho
JH
Kim
Shin Hyoung
SH
Song
Min Jung
MJ
Chang
Ih-Seop
IS
Lee
Ok Sub
OS
Lee
Tae Ryong
TR
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002352:Carrier Proteins; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D015536:Down-Regulation; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism*; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D000070778:Perilipin-1; D000071229:Perilipin-4; D010750:Phosphoproteins / Q000037:antagonists & inhibitors; D034622:RNA Interference; D000072260:RNA Splicing Factors; D029701:Saccharomyces cerevisiae Proteins; D017381:Spliceosomes; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; C079877:PRP19 protein, S cerevisiae; D000070778:Perilipin-1; D000071229:Perilipin-4; D010750:Phosphoproteins; C487119:Plin4 protein, mouse; C518638:Prpf19 protein, mouse; D000072260:RNA Splicing Factors; D029701:Saccharomyces cerevisiae Proteins; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D005992:Glycerol-3-Phosphate O-Acyltransferase; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase