Pathway Map Details
wtCFTR and delta508 traffic / Clathrin coated vesicles formation (norm and CF)
Object list (links open in MetaCore):
CFTR, AP complex 2, AP180, HIP12, SNX9, HIP1, Actin cytoskeletal, Clathrin heavy chain, Myosin VI, Eps15, Epsin 1, DAB2, Actin, Dynamin-2, Endophilin B1, BIN1 (Amphiphysin II), Clathrin, PICALM, Myosin I
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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