title: CFTR anion channel modulates expression of human transmembrane mucin MUC3 through the PDZ protein GOPC.
abstract: The transmembrane mucins in the enterocyte are type 1 transmembrane proteins with long and rigid mucin domains, rich in proline, threonine and serine residues that carry numerous O-glycans. Three of these mucins, MUC3, MUC12 and MUC17 are unique in harboring C-terminal class I PDZ motifs, making them suitable ligands for PDZ proteins. A screening of 123 different human PDZ domains for binding to MUC3 identified a strong interaction with the PDZ protein GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein). This interaction was mediated by the C-terminal PDZ motif of MUC3, binding to the single GOPC PDZ domain. GOPC is also a binding partner for cystic fibrosis transmembrane conductance regulator (CFTR) that directs CFTR for degradation. Overexpression of GOPC downregulated the total levels of MUC3, an effect that was reversed by introducing CFTR. The results suggest that CFTR and MUC3 compete for binding to GOPC, which in turn can regulate levels of these two proteins. For the first time a direct coupling between mucins and the CFTR channel is demonstrated, a finding that will shed further light on the still poorly understood relationship between cystic fibrosis and the mucus phenotype of this disease.
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Thaher
authors.initials: T
authors.lastname: Pelaseyed
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001667:Binding, Competitive / Q000235:genetics; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D006224:Cricetinae; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D025461:Feedback, Physiological; D000077614:Golgi Matrix Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D055263:Mucin-3 / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D050994:Voltage-Dependent Anion Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C434484:GOPC protein, human; D000077614:Golgi Matrix Proteins; C524652:MUC3A protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D055263:Mucin-3; D050994:Voltage-Dependent Anion Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator