Abstract

Cell membranes are fundamental to life, and defects in their function underlie many diseases. Membranes of different organelles have different lipid compositions. For example, cholesterol is markedly enriched in the plasma membrane compared with the ER. Scientists know the enzymes that synthesize and degrade the various lipids in different cell membranes. Yet, very little is known about how these enzymes are regulated so as to maintain differential lipid compositions. Our laboratory made the initial inroad into this problem through the discovery of the SREBP family of transcription factors that control synthesis and uptake of cholesterol and fatty acids. We discovered four proteins whose actions govern the regulated trafficking mechanism that dictates the activities of SREBPs. We are now in a unique position to decipher precisely how this system works at a molecular level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL020948-37
Application #
8462653
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
37
Fiscal Year
2013
Total Cost
$602,732
Indirect Cost
$223,656

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Russell, David W (2018) Lucky, times ten: A career in Texas science. J Biol Chem 293:18804-18827
Que, Xuchu; Hung, Ming-Yow; Yeang, Calvin et al. (2018) Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature 558:301-306
Stender, Stefan; Smagris, Eriks; Lauridsen, Bo K et al. (2018) Relationship between genetic variation at PPP1R3B and levels of liver glycogen and triglyceride. Hepatology 67:2182-2195
Schumacher, Marc M; Jun, Dong-Jae; Johnson, Brittany M et al. (2018) UbiA prenyltransferase domain-containing protein-1 modulates HMG-CoA reductase degradation to coordinate synthesis of sterol and nonsterol isoprenoids. J Biol Chem 293:312-323
Mitsche, Matthew A; Hobbs, Helen H; Cohen, Jonathan C (2018) Patatin-like phospholipase domain-containing protein 3 promotes transfer of essential fatty acids from triglycerides to phospholipids in hepatic lipid droplets. J Biol Chem 293:6958-6968
Banfi, Serena; Gusarova, Viktoria; Gromada, Jesper et al. (2018) Increased thermogenesis by a noncanonical pathway in ANGPTL3/8-deficient mice. Proc Natl Acad Sci U S A 115:E1249-E1258
Fine, Michael; Schmiege, Philip; Li, Xiaochun (2018) Structural basis for PtdInsP2-mediated human TRPML1 regulation. Nat Commun 9:4192
Linden, Albert G; Li, Shili; Choi, Hwa Y et al. (2018) Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res 59:475-487
Johnson, Brittany M; DeBose-Boyd, Russell A (2018) Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase. Semin Cell Dev Biol 81:121-128
Qi, Xiaofeng; Schmiege, Philip; Coutavas, Elias et al. (2018) Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. Science 362:

Showing the most recent 10 out of 766 publications