Accessory Protein Facilitated CFTR-CFTR Interaction, a Molecular Mechanism to Potentiate the Chloride Channel Activity

• Published in: Cell Vol. 103; no. 1; pp. 169 - 179
• Main Authors: Wang, Shusheng, Yue, Hongwen, Derin, Rachel B, Guggino, William B, Li, Min
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.09.2000
• Subjects: Amino Acid Sequence - physiology; Animals; CAP70 protein; Carrier Proteins - chemistry; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Carrier Proteins - pharmacology; Cell Extracts - analysis; Cell Extracts - chemistry; Cell Membrane - metabolism; Cell Membrane - ultrastructure; CFTR gene; Cystic Fibrosis Transmembrane Conductance Regulator - chemistry; Cystic Fibrosis Transmembrane Conductance Regulator - drug effects; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Intestine, Small - cytology; Intestine, Small - metabolism; Kidney - cytology; Kidney - metabolism; Membrane Proteins; Mice; Models, Biological; Molecular Sequence Data; Protein Structure, Tertiary - drug effects; Protein Structure, Tertiary - physiology; transmembrane conductance regulator
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)00096-9

The c ystic f ibrosis t ransmembrane conductance r egulator ( CFTR) gene encodes a chloride channel protein that belongs to the superfamily of A TP b inding c assette (ABC) transporters. Phosphorylation by protein kinase A in the presence of ATP activates the CFTR-mediated chloride conductance of the apical membranes. We have identified a novel hydrophilic CFTR binding protein, CAP70, which is also concentrated on the apical surfaces. CAP70 consists of four PDZ domains, three of which are capable of binding to the CFTR C terminus. Linking at least two CFTR molecules via cytoplasmic C-terminal binding by either multivalent CAP70 or a bivalent monoclonal antibody potentiates the CFTR chloride channel activity. Thus, the CFTR channel can be switched to a more active conducting state via a modification of intermolecular CFTR-CFTR contact that is enhanced by an accessory protein.