Dr. Jeffrey Esko will present a WALS lecture on Wed (9/11/13) from 3pm to 4pm at the Masur Auditorium (Bldg 10) ah the NIH.
Talk title: Proteoglycans: Arbiters of lipoprotein metabolism
Recently, genetic experiments in mice identified the heparan sulfate proteoglycan syndecan-1 as an important receptor for triglyceride-rich lipoprotein (TRL) clearance in the liver. This receptor consists of a protein core and one or more heparan sulfate chains, which make up the binding site for the TRLs. Binding depends on the heparan sulfate chains based on the accumulation of plasma TRLs in mice bearing mutations in heparan sulfate biosynthesis. To identify the major apolipoproteins that mediate binding to the heparan sulfate chains, we developed a series of in vitro and in vivo assays, which led to the identification of apolipoprotein E and apolipoprotein A5 as the relevant ligands on TRLs. Clearance of TRLs through syndecan-1 is atheroprotective based on the increase in atherosclerosis in knock-out mice fed a high-fat diet. Proteoglycans in macrophages also play an atheroprotective role, but not through a clearance mechanism. Instead, one or more proteoglycans on the macrophage keep the cells in a tonic state in response to interferon beta stimulation.