FIGURE 1.

LDLR trafficking in an interconnected membrane system (A) Low-density lipoprotein (LDL) receptor (LDLR) bound to its cargo is internalised via clathrin-mediated endocytosis. Within early endosomes (EE) LDLR separates from LDL and is sorted to recycling endosomes (RE) for transport to the plasma membrane. Receptors that fail to separate from LDL or are marked for degradation by extracellular or intracellular factors remain in the maturing endosomal system, resulting in their degradation in late endosomes and lysosomes (LELs). (B) Membrane contact sites between endoplasmic reticulum (ER) and plasma membrane are lipid exchange routes in both S. cerevisiae and mammalian cells, affecting sterol and PI(4,5)P₂ abundance. In S. cerevisiae sterol transfer to the budding vesicle is important for fission. In mammalian cells PI(4,5)P₂ is shuffled between PM and ER via ORP5 and ORP8 proteins and PM PI(4,5)P₂ pools can be replenished by PI transfer via Nir2, Nir3 and TMEM24. (C) Sorting of LDLR is enhanced by sorting nexin 17 (SNX17) and requires the WASH and COMMD/CCDC22/CCDC93 (CCC) complex for efficient recycling.