wtCFTR and delta508 traffic/ Clathrin coated vesicles
formation (norm and 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 , .
CFTR may be internalizated from plasma membrane in a
Clathrin-dependent manner. The classical key components of
Clathrin-dependent endocytosis of CFTR are Adaptor-related
protein complex 2 (AP complex 2) ,  and Disabled homolog 2 mitogen-responsive phosphoprotein
(Dab2) . In addition, some cargo-unspecified
adaptors may participate in this process , , .
After the Clathrin lattice is formed, dynamins (e.g.,
Dynamin-2), endophilin (e.g., Endophilin
B1), epsins and amphiphysin (e.g., BIN1) are
involved in membrane invagination and Clathrin
rearrangements. The plus-end motor Myosin I pulls the
Dynamin-2 ring in the direction of the cell surface, while
the minus-end motor Myosin VI pulls the coated bud into the
cytosol. The resulting strain could then severe the constricted stalk beneath the dynamin
ring , .
The most common CFTR mutation is the loss of the Phe
residue at position 508 (deltaF508-CFTR).
deltaF508-CFTR membrane expression is reduced compare with
wtCFTR, but clathrin coated vesiales
formation deltaF508-CFTR and
wtCFTR is regulated in similar manner.
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CFTR directly mediates nucleotide-regulated glutathione flux.
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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
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The ABC protein turned chloride channel whose failure causes cystic fibrosis.
Nature 2006 Mar 23;440(7083):477-83
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Endocytic trafficking of CFTR in health and disease.
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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
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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
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Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator.
The Journal of biological chemistry 2004 Sep 3;279(36):38025-31
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Epsins: adaptors in endocytosis?
Nature reviews. Molecular cell biology 2002 Dec;3(12):971-7
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Cargo- and compartment-selective endocytic scaffold proteins.
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Life of a clathrin coat: insights from clathrin and AP structures.
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Endocytosis: clathrin-mediated membrane budding.
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