Pathway maps

Cholesterol and Sphingolipids transport / Recycling to plasma membrane in lung (normal and CF)
Cholesterol and Sphingolipids transport / Recycling to plasma membrane in lung (normal and CF)

Object List (links open in MetaCore):

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 [1], [2]. ERC is thus one of the most Cholesterol -rich compartments in the cell [3].

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 [1], [4], [5].

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 [6], [7]. 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 [8], [9], [10], [11], [12]. 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 [13], [14], [11].

Sphingolipids also recycle via the endocytic recycling compartment [15].


  1. Hao M, Lin SX, Karylowski OJ, Wustner D, McGraw TE, Maxfield FR
    Vesicular and non-vesicular sterol transport in living cells. The endocytic recycling compartment is a major sterol storage organelle. The Journal of biological chemistry 2002 Jan 4;277(1):609-17
  2. Naslavsky N, Rahajeng J, Sharma M, Jovic M, Caplan S
    Interactions between EHD proteins and Rab11-FIP2: a role for EHD3 in early endosomal transport. Molecular biology of the cell 2006 Jan;17(1):163-77
  3. Takahashi M, Murate M, Fukuda M, Sato SB, Ohta A, Kobayashi T
    Cholesterol controls lipid endocytosis through Rab11. Molecular biology of the cell 2007 Jul;18(7):2667-77
  4. Holtta-Vuori M, Ikonen E
    Endosomal cholesterol traffic: vesicular and non-vesicular mechanisms meet. Biochemical Society transactions 2006 Jun;34(Pt 3):392-4
  5. Schroeder F, Atshaves BP, McIntosh AL, Gallegos AM, Storey SM, Parr RD, Jefferson JR, Ball JM, Kier AB
    Sterol carrier protein-2: new roles in regulating lipid rafts and signaling. Biochimica et biophysica acta 2007 Jun;1771(6):700-18
  6. Chen W, Sun Y, Welch C, Gorelik A, Leventhal AR, Tabas I, Tall AR
    Preferential ATP-binding cassette transporter A1-mediated cholesterol efflux from late endosomes/lysosomes. The Journal of biological chemistry 2001 Nov 23;276(47):43564-9
  7. Bates SR, Tao JQ, Collins HL, Francone OL, Rothblat GH
    Pulmonary abnormalities due to ABCA1 deficiency in mice. American journal of physiology. Lung cellular and molecular physiology 2005 Dec;289(6):L980-9
  8. Gadsby DC, Vergani P, Csanady L
    The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 2006 Mar 23;440(7083):477-83
  9. Albrecht C, Viturro E
    The ABCA subfamily--gene and protein structures, functions and associated hereditary diseases. Pflugers Archiv : European journal of physiology 2007 Feb;453(5):581-9
  10. Kobayashi A, Takanezawa Y, Hirata T, Shimizu Y, Misasa K, Kioka N, Arai H, Ueda K, Matsuo M
    Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1. Journal of lipid research 2006 Aug;47(8):1791-802
  11. Ghering AB, Davidson WS
    Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Journal of lipid research 2006 Dec;47(12):2781-8
  12. Yasuhisa K, Shin-ya M, Michinori M, Kazumitsu U
    Mechanism of multidrug recognition by MDR1/ABCB1. Cancer science 2007 Sep;98(9):1303-10
  13. Wang N, Tall AR
    Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux. Arteriosclerosis, thrombosis, and vascular biology 2003 Jul 1;23(7):1178-84
  14. Wang N, Ranalletta M, Matsuura F, Peng F, Tall AR
    LXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhances cholesterol mass efflux to HDL. Arteriosclerosis, thrombosis, and vascular biology 2006 Jun;26(6):1310-6
  15. Hao M, Maxfield FR
    Characterization of rapid membrane internalization and recycling. The Journal of biological chemistry 2000 May 19;275(20):15279-86