wtCFTR and delta508 traffic / Clathrin coated vesicles formation (norm and CF)

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 [1], [2], [3]. Cell surface expression of the CFTR is a highly regulated intracellular process [4], [5].

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) [6], [7] and Disabled homolog 2 mitogen-responsive phosphoprotein (Dab2) [8]. In addition, some cargo-unspecified adaptors may participate in this process [9], [10], [11].

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 [8], [12].

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.

References:

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