EHD3, APOA1, Rab11-FIP2, Sphingolipids extracelular region, <plasma membrane> cholesterol = <extracellular region> cholesterol, <vesicle> Cholesterol = <plasma membrane> Cholesterol, HDL nascent lipids, ABCA1, <vesicle> Sphingolipids = <plasma membrane> Sphingolipids, Cholesterol extracellular region, CFTR, Sphingolipids cytoplasm, Sphingolipids plasma membrane, Cholesterol plasma membrane, ABCG1, Cholesterol vesicle, ABCA7, Caveolin-1, Cholesterol plasma membrane, <cytoplasm> Sphingolipids = <extracellular region> Sphingolipids, <vesicle> Cholesterol = <plasma membrane> Cholesterol, SCPX(SCP2), HDL, Sphingolipids plasma membrane, Sphingolipids vesicle, Rab-11A, Cholesterol plasma membrane
Cholesterol and Sphingolipid transport/ Recycling to plasma membrane in lung (normal and CF)
In lungs, Cholesterol and Sphingolipids move from early endosomes to the endocytic recycling compartment (ERC) via a Rab-dependent mechanism. Oligomerization of EH domain-containing proteins 1 and 3 ( EHD1 and EHD3 ) is necessary for attraction of Rab11 family interacting protein 2 ( Rab11-FIP2 ). These proteins interact with member RAS oncogene family Rab-11A and their interactions regulate traffic of cargo and lipids through perinuclear recycling endosomes , . ERC is thus one of the most Cholesterol -rich compartments in the cell .
Cholesterol can move from the plasma membrane to the ERC and back by a non-vesicular, ATP-independent process. Sterol carrier protein 2 ( SCPX(SCP2) ) carries Cholestero l from internal membranes to plasmalemma, specifically to caveolae-lipid rafts , , .
Soluble cytosolic sterol carrier proteins transport Cholesterol to the inner leaflet of the plasma membrane. ATP-binding cassette family member 1 ( ABCA1 ) activity is crucial for the maintenance of the normal lung lipid composition , . ATP-binding cassette, sub-family G member 1 and sub-family A member 7 ( ABCG1 and ABCA7 ) transports Cholestero l from the inner to outer leaflets enriching the latter , , , , . Specific binding of Apolipoprotein A-I ( APOA1 ) to ABCA1 involves a direct molecular interaction. APOA1 binding to ABCA1 promotes efflux of cellular Cholesterol and phospholipids, likely as a result of coordinated specific transmembrane transport of both lipids by ABCA1 , , .
Sphingolipids also recycle via the endocytic recycling compartment .