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
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
deltaF508-CFTR is disrupted, thus preventing
membrane expression of
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 , , . PIST action is activated by
Syntaxin 6 , (Cheng et al., The 21st annual
north American cystic fibrosis conference, California, 2007) and is inhibited by Ras
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
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