THE YOUNG LABORATORY

        Stephen G. Young, along with two UCLA faculty colleagues (Anne P. Beigneux and Loren G. Fong), identified a GPI-anchored endothelial cell protein, GPIHBP1, that is required for the intravascular processing of triglyceride-rich lipoproteins (TRLs). We went on to show that GPIHBP1 binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles it across endothelial cells to its site of action in the capillary lumen. In the absence of GPIHBP1, LPL remains stranded in the interstitial spaces, and TRL processing is severely impaired. GPIHBP1 is also required for the margination of TRLs along capillaries (allowing LPL-mediated triglyceride processing to proceed). In the absence of GPIHBP1, lipoproteins never stop along capillaries. Along with Michael Ploug (Copenhagen, Denmark), we showed that the binding of GPIHBP1 to LPL preserves the structural integrity of LPL as well as its enzymatic activity. The consequences of LPL deficiency and GPIHBP1 deficiency in humans are identical—impaired TRL processing and severe hypertriglyceridemia. We have identified multiple GPIHBP1 mutations associated with hypertriglyceridemia; all of the mutations abolish the ability of GPIHBP1 to bind LPL. We also identified LPL mutations that abolish the ability of LPL to bind to GPIHBP1. Recently, our group, along with Katsuyuki Nakajima, showed that some acquired cases of hypertriglyceridemia are caused by GPIHBP1 autoantibodies. GPIHBP1 autoantibodies block the ability of GPIHBP1 to capture LPL and escort the enzyme to the capillary lumen. Dr. Young is an elected member of the National Academy of Sciences.
Gonda Bldg. Rm 4506
695 Charles E. Young Drive South
Los Angeles, CA 90095
Phone(310) 267-5856
Fax | (310) 206-0865
 
Principal Investigator
Stephen G. Young
sgyoung@mednet.ucla.edu
 
Collaborators