<extracellular region> Sphingomyelin = <cytoplasm> Sphingomyelin, Sphingolipids, lLDL = cholesterol + cholesteryl ester + phospholipid, Rab-4, IDL lipids, lIDL = triacylglycerols + cholesteryl ester + phospholipid, Rab-5A, LDL lipids, Sphingomyelin plasma membrane, Cholesteryl ester vesicle, <extracellular region> Sphingomyelin = <cytoplasm> Sphingomyelin, <extracellular region> lLDL = <vesicle> lLDL, ARH, Glycosphingolipid plasma membrane, Clathrin, Caveolin-1, DAB2, LDL lipids, Caveolin-2, AP complex 2, <plasma membrane> Glycosphingolipid = <cytoplasm> Glycosphingolipid, IDL lipids, Cholesterol extracellular region, LDLR, Cholesteryl ester extracellular region, Cholesterol vesicle, Dynamin-2, Sphingomyelin, <extracellular region> lIDL = <vesicle> lIDL, Rabenosyn-5, Glycosphingolipid cytoplasm
Cholesterol and Sphingolipid transport/ Influx to the early endosome in lung (normal and CF)
Lung cells absorb Cholesterol preferentially as Cholesteryl ester bound to lipoprotein particles such as Intermediate density lipoproteins ( IDL ) and Low density lipoproteins ( LDL ) [1]. These lipoproteins are recognized by corresponding low density lipoprotein receptor ( LDLR ) [2], [1], [3], [4]. LDLR is internalized into clathrin-coated pits and transported to sorting endosomes. Disabled homolog 2 ( Dab2 ) protein mediates internalization of Low density lipoprotein receptor ( LDLR ) independently of LDL receptor adaptor protein 1 ( ARH ) and the Adaptor-related protein complex 2 ( AP-2 ). If Dab2 is absent, ARH can mediate LDLR endocytosis. This mediation requires AP complex 2 [5], [6].
Sphingolipid -containing membranes are internalized via the caveolae-raft or clathrin-dependent pathways that involve Caveolin-1 [7].
Further lipid sorting from early endosomes to sorting endosomes is mediated by members of the RAS oncogene family Rab-5A and Rab-4 in clathrin vesicles formed from pits. Rab-5 -independent sorting also occurs in caveolae endosomes [8].