wtCFTR and delta508-CFTR traffic / Generic schema (norm and CF)

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wtCFTR and delta508-CFTR traffic/ Generic schema (norm and CF)

The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette transporter superfamily and 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].

The most common CFTR mutation is loss of a Phe residue at position 508 (deltaF508-CFTR). It is recognized as misfolded by the endoplasmic reticulum (ER) quality control machinery and targeted for proteosomal degradation. This leads to inadequate amounts of poorly functioning CFTR reaching the cell membrane to achieve Cl(-) transport [6]. However, growth of deltaF508-CFTR expressing cells at reduced temperature allows the mutant CFTR molecules to exit the ER and reach the cell surface [5].

Export of CFTR from ER to the Golgi may be realized in Coat protein complex-II (COPII)-dependent manner [7], [8]. It is supposed, that binding of COPII to deltaF508-CFTR is disrupted, thus preventing membrane expression of deltaF508-CFTR [9].

A Golgi 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 [10], [11], [12]. PIST action is activated by Syntaxin 6 [13], (Cheng et al., The 21st annual north American cystic fibrosis conference, California, 2007) and is inhibited by Ras homolog gene family, member Q (TC10) [14].

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 [15]. CFTR stabilization in plasma membrane depends on participation of different proteins. For example, Solute carrier family 9 member 3 regulator 1 (EBP50) [16], Copper metabolism domain containing 1 (COMMD1) (Drevillion, L et al., The 21st annual north American cystic fibrosis conference, California, 2007), Protein kinase C epsilon (PKC-epsilon) [17] Filamin A and Filamin B [18] and cAMP-dependent protein kinase (PKA) stabilize CFTR [19]. Syntaxin 1A/ Synaptosomal-associated protein 23kDa (SNAP-23) have negative influence on CFTR membrane expression [19], [20].

CFTR may be internalizated from plasma membrane in Clathrin-dependent manner. The classical key components of Clathrin-dependent endocytosis of CFTR are Adaptor-related protein complex 2 (AP complex 2) [21], [22] and Disabled homolog 2 mitogen-responsive phosphoprotein (Dab2) [23]. In addition, some cargo-unspecified adaptors may participate in this process [24], [25], [26].

Next phase is the fusion of coated-pit-derived primary endocytic vesicles with sorting endosomes. It is regulated,for example,. by a member of RAS oncogene family Rab-5A [27], [28] and Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) [29], [30].

At this phase quality control at early endosome may eliminate deltaF508-CFTR too. Components of the Ub-dependent endosomal sorting machinery Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), Signal transducing adaptor molecule 2 (STAM2), Tumor susceptibility gene 101 (TSG101), Vacuolar protein sorting 25 homolog (Vps25) and Chromatin modifying protein 4B (CHMP4B) are selectively bound to deltaF508-CFTR and stimulate lysosomal degradation of the misfolded CFTR [31].

The maturation of sorting endosomes to late endosomes is facilitated by a member of the RAS oncogene family Rab7 via an unknown mechanism [28], [32], [33].

Late endosomes may participate in fusion with the other late endosomes or lysosome via SNARE-mediated mechanism [30], [34], [35]. In addition, Rab7 is directly involved in the aggregation and fusion of late endocytic structures/lysosomes [36], [37].

Rab GTPase Rab-27A, which plays a pivotal role in secretions and lysosomal degradation, negatively regulates CFTR channel activity by physically interacting with it and impairing it from reaching the plasma membrane, thus increasing internal or cytosolic CFTR pool [38], [39].

Moreover, CFTR may be delivered to the cell surface via the shot pathway from endosomes via different recycling endosomes [5], [29]. It is realized mainly via Rab-4 and/or Rab-11A-dependent mechanisms [39].

Endogenous Rab-11A, a member of RAS oncogene family, forms a complex with Myosin Vb which facilitates recycling of CFTR from recycling endosomes to the apical plasma membrane in polarized epithelial cells [40], [41], [42]. Rab-4 protein group belongs to RAS oncogene family which controls recycling events from endosome to the plasma membrane, fusion, and degradation inhibits CFTR chloride channel activity by diminishing its cell surface expression [43].

It was shown that regulation of expression or activity of some member CFTR traffic pathway may lead to the membrane expression of deltaF508-CFTR. For example, over-regulation of Rab-11A [28], EBP50 [44] and down-regulation Rab-5A, Rab-7 [28] and Syntaxin 6 (Cheng et al., The 21st annual north American cystic fibrosis conference, California, 2007) have this effect.

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. Dubin PJ, McAllister F, Kolls JK
    Is cystic fibrosis a TH17 disease? Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2007 Jun;56(6):221-7
  7. 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
  8. Gurkan 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
  9. Wang X, Matteson J, An Y, Moyer B, Yoo JS, Bannykh S, Wilson IA, Riordan JR, Balch WE
    COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code. The Journal of cell biology 2004 Oct 11;167(1):65-74
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. Haggie PM, Stanton BA, Verkman AS
    Increased diffusional mobility of CFTR at the plasma membrane after deletion of its C-terminal PDZ binding motif. The Journal of biological chemistry 2004 Feb 13;279(7):5494-500
  17. Auerbach M, Liedtke CM
    Role of the scaffold protein RACK1 in apical expression of CFTR. American journal of physiology. Cell physiology 2007 Jul;293(1):C294-304
  18. Thelin WR, Chen Y, Gentzsch M, Kreda SM, Sallee JL, Scarlett CO, Borchers CH, Jacobson K, Stutts MJ, Milgram SL
    Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR. The Journal of clinical investigation 2007 Feb;117(2):364-74
  19. Chang SY, Di A, Naren AP, Palfrey HC, Kirk KL, Nelson DJ
    Mechanisms of CFTR regulation by syntaxin 1A and PKA. Journal of cell science 2002 Feb 15;115(Pt 4):783-91
  20. Cormet-Boyaka E, Di A, Chang SY, Naren AP, Tousson A, Nelson DJ, Kirk KL
    CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex. Proceedings of the National Academy of Sciences of the United States of America 2002 Sep 17;99(19):12477-82
  21. Weixel KM, Bradbury NA
    The carboxyl terminus of the cystic fibrosis transmembrane conductance regulator binds to AP-2 clathrin adaptors. The Journal of biological chemistry 2000 Feb 4;275(5):3655-60
  22. Weixel KM, Bradbury NA
    Mu 2 binding directs the cystic fibrosis transmembrane conductance regulator to the clathrin-mediated endocytic pathway. The Journal of biological chemistry 2001 Dec 7;276(49):46251-9
  23. Swiatecka-Urban A, Boyd C, Coutermarsh B, Karlson KH, Barnaby R, Aschenbrenner L, Langford GM, Hasson T, Stanton BA
    Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator. The Journal of biological chemistry 2004 Sep 3;279(36):38025-31
  24. Wendland B
    Epsins: adaptors in endocytosis? Nature reviews. Molecular cell biology 2002 Dec;3(12):971-7
  25. Szymkiewicz I, Shupliakov O, Dikic I
    Cargo- and compartment-selective endocytic scaffold proteins. The Biochemical journal 2004 Oct 1;383(Pt 1):1-11
  26. Edeling MA, Smith C, Owen D
    Life of a clathrin coat: insights from clathrin and AP structures. Nature reviews. Molecular cell biology 2006 Jan;7(1):32-44
  27. Woodman PG
    Biogenesis of the sorting endosome: the role of Rab5. Traffic (Copenhagen, Denmark) 2000 Sep;1(9):695-701
  28. 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
  29. Maxfield FR, McGraw TE
    Endocytic recycling. Nature reviews. Molecular cell biology 2004 Feb;5(2):121-32
  30. Hong W
    SNAREs and traffic. Biochimica et biophysica acta 2005 Jun 30;1744(2):120-44
  31. 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
  32. 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
  33. Somsel Rodman J, Wandinger-Ness A
    Rab GTPases coordinate endocytosis. Journal of cell science 2000 Jan;113 Pt 2:183-92
  34. Bilan F, Thoreau V, Nacfer M, Derand R, Norez C, Cantereau A, Garcia M, Becq F, Kitzis A
    Syntaxin 8 impairs trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits its channel activity. Journal of cell science 2004 Apr 15;117(Pt 10):1923-35
  35. Pryor PR, Mullock BM, Bright NA, Lindsay MR, Gray SR, Richardson SC, Stewart A, James DE, Piper RC, Luzio JP
    Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO reports 2004 Jun;5(6):590-5
  36. Bucci C, Thomsen P, Nicoziani P, McCarthy J, van Deurs B
    Rab7: a key to lysosome biogenesis. Molecular biology of the cell 2000 Feb;11(2):467-80
  37. Stein MP, Feng Y, Cooper KL, Welford AM, Wandinger-Ness A
    Human VPS34 and p150 are Rab7 interacting partners. Traffic (Copenhagen, Denmark) 2003 Nov;4(11):754-71
  38. Saxena SK, Kaur S
    Rab27a negatively regulates CFTR chloride channel function in colonic epithelia: involvement of the effector proteins in the regulatory mechanism. Biochemical and biophysical research communications 2006 Jul 21;346(1):259-67
  39. Saxena SK, Kaur S
    Regulation of epithelial ion channels by Rab GTPases. Biochemical and biophysical research communications 2006 Dec 22;351(3):582-7
  40. Picciano JA, Ameen N, Grant BD, Bradbury NA
    Rme-1 regulates the recycling of the cystic fibrosis transmembrane conductance regulator. American journal of physiology. Cell physiology 2003 Nov;285(5):C1009-18
  41. Swiatecka-Urban A, Brown A, Moreau-Marquis S, Renuka J, Coutermarsh B, Barnaby R, Karlson KH, Flotte TR, Fukuda M, Langford GM, Stanton BA
    The short apical membrane half-life of rescued {Delta}F508-cystic fibrosis transmembrane conductance regulator (CFTR) results from accelerated endocytosis of {Delta}F508-CFTR in polarized human airway epithelial cells. The Journal of biological chemistry 2005 Nov 4;280(44):36762-72
  42. Swiatecka-Urban A, Talebian L, Kanno E, Moreau-Marquis S, Coutermarsh B, Hansen K, Karlson KH, Barnaby R, Cheney RE, Langford GM, Fukuda M, Stanton BA
    Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells. The Journal of biological chemistry 2007 Aug 10;282(32):23725-36
  43. Saxena SK, Kaur S, George C
    Rab4GTPase modulates CFTR function by impairing channel expression at plasma membrane. Biochemical and biophysical research communications 2006 Mar 3;341(1):184-91
  44. Bossard F, Robay A, Toumaniantz G, Dahimene S, Becq F, Merot J, Gauthier C
    NHE-RF1 protein rescues DeltaF508-CFTR function. American journal of physiology. Lung cellular and molecular physiology 2007 May;292(5):L1085-94

  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. Dubin PJ, McAllister F, Kolls JK
    Is cystic fibrosis a TH17 disease? Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2007 Jun;56(6):221-7
  7. 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
  8. Gurkan 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
  9. Wang X, Matteson J, An Y, Moyer B, Yoo JS, Bannykh S, Wilson IA, Riordan JR, Balch WE
    COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code. The Journal of cell biology 2004 Oct 11;167(1):65-74
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. Haggie PM, Stanton BA, Verkman AS
    Increased diffusional mobility of CFTR at the plasma membrane after deletion of its C-terminal PDZ binding motif. The Journal of biological chemistry 2004 Feb 13;279(7):5494-500
  17. Auerbach M, Liedtke CM
    Role of the scaffold protein RACK1 in apical expression of CFTR. American journal of physiology. Cell physiology 2007 Jul;293(1):C294-304
  18. Thelin WR, Chen Y, Gentzsch M, Kreda SM, Sallee JL, Scarlett CO, Borchers CH, Jacobson K, Stutts MJ, Milgram SL
    Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR. The Journal of clinical investigation 2007 Feb;117(2):364-74
  19. Chang SY, Di A, Naren AP, Palfrey HC, Kirk KL, Nelson DJ
    Mechanisms of CFTR regulation by syntaxin 1A and PKA. Journal of cell science 2002 Feb 15;115(Pt 4):783-91
  20. Cormet-Boyaka E, Di A, Chang SY, Naren AP, Tousson A, Nelson DJ, Kirk KL
    CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex. Proceedings of the National Academy of Sciences of the United States of America 2002 Sep 17;99(19):12477-82
  21. Weixel KM, Bradbury NA
    The carboxyl terminus of the cystic fibrosis transmembrane conductance regulator binds to AP-2 clathrin adaptors. The Journal of biological chemistry 2000 Feb 4;275(5):3655-60
  22. Weixel KM, Bradbury NA
    Mu 2 binding directs the cystic fibrosis transmembrane conductance regulator to the clathrin-mediated endocytic pathway. The Journal of biological chemistry 2001 Dec 7;276(49):46251-9
  23. Swiatecka-Urban A, Boyd C, Coutermarsh B, Karlson KH, Barnaby R, Aschenbrenner L, Langford GM, Hasson T, Stanton BA
    Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator. The Journal of biological chemistry 2004 Sep 3;279(36):38025-31
  24. Wendland B
    Epsins: adaptors in endocytosis? Nature reviews. Molecular cell biology 2002 Dec;3(12):971-7
  25. Szymkiewicz I, Shupliakov O, Dikic I
    Cargo- and compartment-selective endocytic scaffold proteins. The Biochemical journal 2004 Oct 1;383(Pt 1):1-11
  26. Edeling MA, Smith C, Owen D
    Life of a clathrin coat: insights from clathrin and AP structures. Nature reviews. Molecular cell biology 2006 Jan;7(1):32-44
  27. Woodman PG
    Biogenesis of the sorting endosome: the role of Rab5. Traffic (Copenhagen, Denmark) 2000 Sep;1(9):695-701
  28. 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
  29. Maxfield FR, McGraw TE
    Endocytic recycling. Nature reviews. Molecular cell biology 2004 Feb;5(2):121-32
  30. Hong W
    SNAREs and traffic. Biochimica et biophysica acta 2005 Jun 30;1744(2):120-44
  31. 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
  32. 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
  33. Somsel Rodman J, Wandinger-Ness A
    Rab GTPases coordinate endocytosis. Journal of cell science 2000 Jan;113 Pt 2:183-92
  34. Bilan F, Thoreau V, Nacfer M, Derand R, Norez C, Cantereau A, Garcia M, Becq F, Kitzis A
    Syntaxin 8 impairs trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) and inhibits its channel activity. Journal of cell science 2004 Apr 15;117(Pt 10):1923-35
  35. Pryor PR, Mullock BM, Bright NA, Lindsay MR, Gray SR, Richardson SC, Stewart A, James DE, Piper RC, Luzio JP
    Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO reports 2004 Jun;5(6):590-5
  36. Bucci C, Thomsen P, Nicoziani P, McCarthy J, van Deurs B
    Rab7: a key to lysosome biogenesis. Molecular biology of the cell 2000 Feb;11(2):467-80
  37. Stein MP, Feng Y, Cooper KL, Welford AM, Wandinger-Ness A
    Human VPS34 and p150 are Rab7 interacting partners. Traffic (Copenhagen, Denmark) 2003 Nov;4(11):754-71
  38. Saxena SK, Kaur S
    Rab27a negatively regulates CFTR chloride channel function in colonic epithelia: involvement of the effector proteins in the regulatory mechanism. Biochemical and biophysical research communications 2006 Jul 21;346(1):259-67
  39. Saxena SK, Kaur S
    Regulation of epithelial ion channels by Rab GTPases. Biochemical and biophysical research communications 2006 Dec 22;351(3):582-7
  40. Picciano JA, Ameen N, Grant BD, Bradbury NA
    Rme-1 regulates the recycling of the cystic fibrosis transmembrane conductance regulator. American journal of physiology. Cell physiology 2003 Nov;285(5):C1009-18
  41. Swiatecka-Urban A, Brown A, Moreau-Marquis S, Renuka J, Coutermarsh B, Barnaby R, Karlson KH, Flotte TR, Fukuda M, Langford GM, Stanton BA
    The short apical membrane half-life of rescued {Delta}F508-cystic fibrosis transmembrane conductance regulator (CFTR) results from accelerated endocytosis of {Delta}F508-CFTR in polarized human airway epithelial cells. The Journal of biological chemistry 2005 Nov 4;280(44):36762-72
  42. Swiatecka-Urban A, Talebian L, Kanno E, Moreau-Marquis S, Coutermarsh B, Hansen K, Karlson KH, Barnaby R, Cheney RE, Langford GM, Fukuda M, Stanton BA
    Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells. The Journal of biological chemistry 2007 Aug 10;282(32):23725-36
  43. Saxena SK, Kaur S, George C
    Rab4GTPase modulates CFTR function by impairing channel expression at plasma membrane. Biochemical and biophysical research communications 2006 Mar 3;341(1):184-91
  44. Bossard F, Robay A, Toumaniantz G, Dahimene S, Becq F, Merot J, Gauthier C
    NHE-RF1 protein rescues DeltaF508-CFTR function. American journal of physiology. Lung cellular and molecular physiology 2007 May;292(5):L1085-94

Target Details

Click on a target from the pathway image to view related information.