Pathway Map Details

Normal wtCFTR traffic / Sorting endosome formation



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Rabenosyn-5, Rabaptin-5, Rab-7, VPS45A, 2.7.1.137, 1-(1,2-diacyl-glycerol 3-phospho)-inositol 3-phosphate, PI3K cat class III, CFTR, PI3K reg class III, RABGEF1, VAMP2, Rab-5A, Syntaxin 12, CFTR, 1,2-diacyl-glycerol 3-phosphoinositol, Ubiquitin, EEA1, SNAP-25, NSF

Description:

Normal wtCFTR traffic/ Sorting endosome formation

The cystic fibrosis transmembrane conductance regulator ( CFTR ) is a member of the ATP-binding cassette transporter superfamily. It acts in apical part of the epithelial cells as a plasma-membrane cyclic AMP-activated chloride anion, bicarbonate anion and glutathione channel [1], [2], [3]. Cell surface expression of the CFTR is a highly regulated intracellular process [4], [5].

CFTR internalization from plasma membrane is a very important step in CFTR regulation. CFTR may be internalizated from plasma membrane in a clathrin-dependent manner. Then the coated-pit-derived primary endocytic vesicles are fused with the sorting endosomes. The fusion event is regulated by a member of RAS oncogene family Rab-5A, Early endosome antigen 1 ( EEA1 ) [6], [7] and Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) [8], [9].

Some wtCFTR is transported from the sorting endosome to the lysosome in Ub-dependent manner and is degraded [10].

The maturation of sorting endosomes to the late endosomes is realized with participation of a member of the RAS oncogene family Rab7 via unknown mechanism [11], [12], [7].

References:

  1. Kogan I, Ramjeesingh M, Li C, Kidd JF, Wang Y, Leslie EM, Cole SP, Bear CE
    CFTR directly mediates nucleotide-regulated glutathione flux. The EMBO journal 2003 May 1;22(9):1981-9
  2. Chan HC, Shi QX, Zhou CX, Wang XF, Xu WM, Chen WY, Chen AJ, Ni Y, Yuan YY
    Critical role of CFTR in uterine bicarbonate secretion and the fertilizing capacity of sperm. Molecular and cellular endocrinology 2006 May 16;250(1-2):106-13
  3. 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
  4. Guggino WB, Stanton BA
    New insights into cystic fibrosis: molecular switches that regulate CFTR. Nature reviews. Molecular cell biology 2006 Jun;7(6):426-36
  5. Ameen N, Silvis M, Bradbury NA
    Endocytic trafficking of CFTR in health and disease. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2007 Jan;6(1):1-14
  6. Woodman PG
    Biogenesis of the sorting endosome: the role of Rab5. Traffic (Copenhagen, Denmark) 2000 Sep;1(9):695-701
  7. Gentzsch M, Chang XB, Cui L, Wu Y, Ozols VV, Choudhury A, Pagano RE, Riordan JR
    Endocytic trafficking routes of wild type and DeltaF508 cystic fibrosis transmembrane conductance regulator. Molecular biology of the cell 2004 Jun;15(6):2684-96
  8. Maxfield FR, McGraw TE
    Endocytic recycling. Nature reviews. Molecular cell biology 2004 Feb;5(2):121-32
  9. Hong W
    SNAREs and traffic. Biochimica et biophysica acta 2005 Jun 30;1744(2):120-44
  10. Sharma M, Pampinella F, Nemes C, Benharouga M, So J, Du K, Bache KG, Papsin B, Zerangue N, Stenmark H, Lukacs GL
    Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes. The Journal of cell biology 2004 Mar 15;164(6):923-33
  11. Feng Y, Press B, Wandinger-Ness A
    Rab 7: an important regulator of late endocytic membrane traffic. The Journal of cell biology 1995 Dec;131(6 Pt 1):1435-52
  12. Somsel Rodman J, Wandinger-Ness A
    Rab GTPases coordinate endocytosis. Journal of cell science 2000 Jan;113 Pt 2:183-92