Rader - Figure 11 - LDL Receptor Pathway

The Figure illustrates the transformations the LDL receptor undergoes through its metabolic cycle. The LDL receptor is transported to the cell surface where it clusters in clathrin coated pits. Circulating LDL-C binds to the LDL receptor, which is then internalized so that it delivers the LDL-C to the lysosome, following which (although not shown in the Figure) the receptor recycles back to the cell surface. The LDL receptor makes multiple itineraries from plasma membrane to endosome and then back to the cell surface, continually binding LDL-C and delivering it to the lysosome for hydrolysis and degradation.

The Figure also illustrates the multiple different types of LDL receptor mutations that have different effects on LDL processing:

Class I - the LDL receptor is not made at all;
Class II - the LDL receptor cannot be transported appropriately;
Class III - the LDL receptor does not bind LDL-C appropriately;
Class IV - the LDL receptor does not cluster appropriately;
Class V - the LDL receptor is not recycled back.

The details of these different mutations are not important to explain here, except insofar as they illustrate how different types of mutations in the LDL receptor affect its functional roles in different ways. This is important because ultimately these differences impact on the levels of circulating LDL-C and even on the outcomes in terms of cardiovascular events.

Rader J Clin Lipidol. 2012;