Cholesterol and Sphingolipids transport / Influx to the early endosome in lung (normal and CF)

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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) [1], [2], [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].

References:

  1. Kwiterovich PO Jr
    The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review. The American journal of cardiology 2000 Dec 21;86(12A):5L-10L
  2. Truong TQ, Falstrault L, Tremblay C, Brissette L
    Low density lipoprotein-receptor plays a major role in the binding of very low density lipoproteins and their remnants on HepG2 cells. The international journal of biochemistry & cell biology 1999 Jun;31(6):695-705
  3. Michaely P, Zhao Z, Li WP, Garuti R, Huang LJ, Hobbs HH, Cohen JC
    Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR. The EMBO journal 2007 Jul 25;26(14):3273-82
  4. Tall AR
    Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. Journal of internal medicine 2008 Mar;263(3):256-73
  5. Keyel PA, Mishra SK, Roth R, Heuser JE, Watkins SC, Traub LM
    A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Molecular biology of the cell 2006 Oct;17(10):4300-17
  6. Maurer ME, Cooper JA
    The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. Journal of cell science 2006 Oct 15;119(Pt 20):4235-46
  7. Choudhury A, Dominguez M, Puri V, Sharma DK, Narita K, Wheatley CL, Marks DL, Pagano RE
    Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. The Journal of clinical investigation 2002 Jun;109(12):1541-50
  8. Sharma DK, Choudhury A, Singh RD, Wheatley CL, Marks DL, Pagano RE
    Glycosphingolipids internalized via caveolar-related endocytosis rapidly merge with the clathrin pathway in early endosomes and form microdomains for recycling. The Journal of biological chemistry 2003 Feb 28;278(9):7564-72

  1. Kwiterovich PO Jr
    The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: a current review. The American journal of cardiology 2000 Dec 21;86(12A):5L-10L
  2. Truong TQ, Falstrault L, Tremblay C, Brissette L
    Low density lipoprotein-receptor plays a major role in the binding of very low density lipoproteins and their remnants on HepG2 cells. The international journal of biochemistry & cell biology 1999 Jun;31(6):695-705
  3. Michaely P, Zhao Z, Li WP, Garuti R, Huang LJ, Hobbs HH, Cohen JC
    Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR. The EMBO journal 2007 Jul 25;26(14):3273-82
  4. Tall AR
    Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. Journal of internal medicine 2008 Mar;263(3):256-73
  5. Keyel PA, Mishra SK, Roth R, Heuser JE, Watkins SC, Traub LM
    A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Molecular biology of the cell 2006 Oct;17(10):4300-17
  6. Maurer ME, Cooper JA
    The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. Journal of cell science 2006 Oct 15;119(Pt 20):4235-46
  7. Choudhury A, Dominguez M, Puri V, Sharma DK, Narita K, Wheatley CL, Marks DL, Pagano RE
    Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. The Journal of clinical investigation 2002 Jun;109(12):1541-50
  8. Sharma DK, Choudhury A, Singh RD, Wheatley CL, Marks DL, Pagano RE
    Glycosphingolipids internalized via caveolar-related endocytosis rapidly merge with the clathrin pathway in early endosomes and form microdomains for recycling. The Journal of biological chemistry 2003 Feb 28;278(9):7564-72

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