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Lipoproteins are spherical molecules made up of fat and proteins that play a crucial role in transporting lipids, such as cholesterol and triglycerides, from the liver to other tissues in the body. Anton Potapenko of the University of Zurich, and a team in Switzerland recently published a in the Journal of Lipid Research detailing structural characteristics of the scavenger receptor B1, or SCARB1, a protein that mediates lipid exchange between many cell types and facilitates uptake of high density lipoproteins, or HDL, and low density lipoproteins, or LDL, in some cell types. The gene encoding SCARB1 produces two major splice variants that share structural similarities but differ in their carboxy-terminal domains. Researchers wanted to understand if these splice variants play different roles in the cellular uptake of LDL and HDL by endothelial cells.

Illustration of a low density lipoprotein particle.

The researchers examined cultured endothelial cells to understand how expression of the two SCARB1 variants affected the binding, uptake and trafficking of lipoproteins. They found that variants 1 and 2 localized to the cell surface, and endosomes and lysosomes, respectively. Overexpression of variant 1 increased both HDL and LDL binding and uptake. However, overexpression of variant 2 also increased the uptake of either lipoprotein, but not via surface binding. Therefore, the researchers concluded that variant 2 facilitates lipoprotein uptake indirectly by regulatory and indirect mechanisms.

The study suggests that the two major splice variants of SCARB1 facilitate transendothelial transport of HDL and LDL by different mechanisms, either dependent or independent of the adapter proteins. Because of the limitations of overexpression, it will be important to examine how eliminating each SCARB1 splice variant affects cellular lipid metabolism and lipoprotein trafficking.