Pathway Map Details
Delta508-CFTR traffic / ER-to-Golgi in CF
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Delta508-CFTR traffic/ ER-to-Golgi in CF
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 , , . Cell surface expression of the CFTR is a highly regulated intracellular process , .
The most common CFTR mutation is the 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 . However, growth of deltaF508 -CFTR expressing cells at reduced temperature allows the mutant CFTR molecules to exit the ER and reach the cell surface .
Export of CFTR from ER to the Golgi may be realized in Coat protein complex-II ( COPII )-dependent manner , . It is supposed that binding of COPII to deltaF508 -CFTR is disrupted, thus preventing membrane expression of deltaF508 -CFTR .
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 , , . PIST action is activated by Syntaxin 6 , (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 ) .
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 .
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