Pathway maps

Normal wtCFTR traffic / ER-to-Golgi
Normal wtCFTR traffic / ER-to-Golgi

Object List (links open in MetaCore):

SAR1A, PIST (CAL), CFTR, Syntaxin 6, COPII, Sec31, SAR1, PREB, Coatomer, Sec24, TC10, Sec23, SEC13L, CFTR


Normal wtCFTR traffic/ ER-to-Golgi

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].

Export of CFTR from ER to the Golgi may be realized in Coat protein complex-II ( COPII )-dependent manner [6], [7].

A G olgi associated PDZ and coiled-coil motif containing ( PIST ) regulates CFTR trafficking. PIST causes a reduction in the number of CFTR channels in the plasma membrane and facilitates trafficking of CFTR to lysosomes [8], [9], [10]. PIST action is activated by Syntaxin 6 [11], (Cheng et al., The 21st annual north American cystic fibrosis conference, California, 2007 ) and is inhibited by R as homolog gene family, member Q ( TC10 ) [12].

CFTR modified in ER and/or Golgi may be delivered from the Golgi to the apical membrane, possibly, with participation of coat protein complex Coatomer [13].


  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. Yoo JS, Moyer BD, Bannykh S, Yoo HM, Riordan JR, Balch WE
    Non-conventional trafficking of the cystic fibrosis transmembrane conductance regulator through the early secretory pathway. The Journal of biological chemistry 2002 Mar 29;277(13):11401-9
  7. G-Xrkan C, Stagg SM, Lapointe P, Balch WE
    The COPII cage: unifying principles of vesicle coat assembly. Nature reviews. Molecular cell biology 2006 Oct;7(10):727-38
  8. Cheng J, Moyer BD, Milewski M, Loffing J, Ikeda M, Mickle JE, Cutting GR, Li M, Stanton BA, Guggino WB
    A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression. The Journal of biological chemistry 2002 Feb 1;277(5):3520-9
  9. Cheng J, Wang H, Guggino WB
    Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain protein CAL. The Journal of biological chemistry 2004 Jan 16;279(3):1892-8
  10. Guggino WB
    The cystic fibrosis transmembrane regulator forms macromolecular complexes with PDZ domain scaffold proteins. Proceedings of the American Thoracic Society 2004;1(1):28-32
  11. Charest A, Lane K, McMahon K, Housman DE
    Association of a novel PDZ domain-containing peripheral Golgi protein with the Q-SNARE (Q-soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor) protein syntaxin 6. The Journal of biological chemistry 2001 Aug 3;276(31):29456-65
  12. Cheng J, Wang H, Guggino WB
    Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10. The Journal of biological chemistry 2005 Feb 4;280(5):3731-9
  13. Godi A, Di Campli A, Konstantakopoulos A, Di Tullio G, Alessi DR, Kular GS, Daniele T, Marra P, Lucocq JM, De Matteis MA
    FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nature cell biology 2004 May;6(5):393-404