wtCFTR and deltaF508 traffic/ Late endosome and Lysosome
(norm and CF)
The cystic fibrosis transmembrane conductance regulator
(CFTR) is a member of the ATP-binding cassette transporter
superfamily. It acts in the 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 , .
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 coated-pit-derived primary endocytic vesicles are fused with sorting
endosomes. The maturation of sorting endosomes to late endosomes is realized with
participation of a member of the RAS oncogene family Rab7
via an unknown mechanism , , .
Late endosomes may fuse with other late endosomes or the lysosome via SNARE-mediated
mechanism , , . In addition,
Rab7 is directly involved in the aggregation and fusion of
late endocytic structures/lysosomes , .
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 an internal or cytosolic
CFTR pool, whereas Synaptotagmin-like 5
CFTR ability to interact with
Rab-27A and may rescue it via competition with
The most common CFTR mutation is the loss of a Phe
residue at position 508
deltaF508-CFTR membrane expression is reduced compare
with wtCFTR and its lysosomal
degradation is realized in the same way as
wtCFTR, although more
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