Approaches to Visualising Endocytosis of LDL-Related Lipoproteins

Abstract

Endocytosis is the process by which molecules are actively transported into cells. It can take on a variety of forms depending on the cellular machinery involved ranging from specific receptor-mediated endocytosis to the less selective and actin-driven macropinocytosis. The plasma lipoproteins, which deliver lipids and other cargo to cells, have been intensely studied with respect to their endocytic uptake. One of the first molecules to be visualised undergoing endocytosis via a receptor-mediated, clathrin-dependent pathway was low-density lipoprotein (LDL). The LDL molecule has subsequently been shown to be internalised through multiple endocytic pathways. Dissecting the pathways of lipoprotein endocytosis has been crucial to understanding the regulation of plasma lipid levels and how lipids enter cells in the arterial wall to promote atherosclerosis. It has also aided understanding of the dysregulation that occurs in plasma lipid levels when molecules involved in uptake are defective, as is the case in familial hypercholesterolemia (FH). The aim of this review is to outline the many endocytic pathways utilised for lipoprotein uptake. It explores the various experimental approaches that have been applied to visualise lipoprotein endocytosis with an emphasis on LDL and its more complex counterpart, lipoprotein(a) [Lp(a)]. Finally, we look at new developments in lipoprotein visualisation that hold promise for scrutinising endocytic pathways to finer detail in the future.

High-Density Lipoprotein Subfractions Remodeling: A Critical Process for the Treatment of Atherosclerotic Cardiovascular Diseases

“…56 The complex enters the cytoplasm through the invagination of the cell membrane to form vesicles, and the lipid component of LDL/VLDL is hydrolyzed by enzymes in the lysosome thereby indirectly removing HDL-CEs. 57 Approximately 33% of CEs in HDL are delivered to the liver for selective uptake by SR-BI. 56 Hepatic cholesterol can be excreted into the bile, which is either reabsorbed by the intestine or ultimately excreted in feces.…”

Fatty acid uptake in Trypanosoma brucei: Host resources and possible mechanisms

“…Receptor-mediated binding and cell-anchoring of lipoprotein particles can facilitate selective uptake of lipids, such as cholesteryl esters, directly into the cell without uptake of the whole particle ( Seo et al., 2005 ). Conversely, uptake of whole serum lipoproteins by receptor-mediated endocytosis can provide fatty acids through breakdown of internalized phospholipid, TAGs, and cholesteryl ester cargo ( Siddiqui et al., 2022 ). Albumin, along with its bound fatty acids, can also be internalized via a number of cell surface receptors, which direct albumin recycling, trafficking, and degradation ( Sleep et al., 2013 ).…”

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

“…Eukaryotic cells take up molecules, such as extracellular proteins and lipoproteins, by a process called endocytosis, which includes clathrin-dependent or -independent endocytosis and micropinocytosis ( Figure 2 ) [ 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 ]. In clathrin-dependent endocytosis, when a ligand molecule binds to a receptor on the plasma membrane, a clathrin molecule binds to the cytosol via an AP2 adaptor protein, and a ball-shaped structure of the plasma membrane is formed [ 270 , 271 , 272 , 273 ].…”