title: COMMD1-mediated ubiquitination regulates CFTR trafficking.
abstract: The CFTR (cystic fibrosis transmembrane conductance regulator) protein is a large polytopic protein whose biogenesis is inefficient. To better understand the regulation of CFTR processing and trafficking, we conducted a genetic screen that identified COMMD1 as a new CFTR partner. COMMD1 is a protein associated with multiple cellular pathways, including the regulation of hepatic copper excretion, sodium uptake through interaction with ENaC (epithelial sodium channel) and NF-kappaB signaling. In this study, we show that COMMD1 interacts with CFTR in cells expressing both proteins endogenously. This interaction promotes CFTR cell surface expression as assessed by biotinylation experiments in heterologously expressing cells through regulation of CFTR ubiquitination. In summary, our data demonstrate that CFTR is protected from ubiquitination by COMMD1, which sustains CFTR expression at the plasma membrane. Thus, increasing COMMD1 expression may provide an approach to simultaneously inhibit ENaC absorption and enhance CFTR trafficking, two major issues in cystic fibrosis.
authors.affiliation: INSERM, Unité U955, Créteil, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Drévillon
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Tanguy
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hinzpeter
authors.forename: Nicole
authors.initials: N
authors.lastname: Arous
authors.forename: Alix
authors.initials: A
authors.lastname: de Becdelièvre
authors.forename: Abdel
authors.initials: A
authors.lastname: Aissat
authors.forename: Agathe
authors.initials: A
authors.lastname: Tarze
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Pascale
authors.initials: P
authors.lastname: Fanen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019921:Biotinylation; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering; D054875:Ubiquitination / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480519:COMMD1 protein, human; D002352:Carrier Proteins; D034741:RNA, Small Interfering; D019005:Cystic Fibrosis Transmembrane Conductance Regulator