title: Double-membrane gap junction internalization requires the clathrin-mediated endocytic machinery.
abstract: Direct cell-cell communication mediated by plasma membrane-spanning gap junction (GJ) channels is vital to all aspects of cellular life. Obviously, GJ intercellular communication (GJIC) requires precise regulation, and it is known that controlled biosynthesis and degradation, and channel opening and closing (gating) are exploited. We discovered that cells internalize GJs in response to various stimuli. Here, we report that GJ internalization is a clathrin-mediated endocytic process that utilizes the vesicle-coat protein clathrin, the adaptor proteins adaptor protein complex 2 and disabled 2, and the GTPase dynamin. To our knowledge, we are first to report that the endocytic clathrin machinery can internalize double-membrane vesicles into cells.
authors.affiliation: Department of Biological Sciences, Lehigh University, 111 Research Drive, Bethlehem, PA 18015, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Gumpert
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Varco
authors.forename: Susan M
authors.initials: SM
authors.lastname: Baker
authors.forename: Michelle
authors.initials: M
authors.lastname: Piehl
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Falk
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D002450:Cell Communication; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D018031:Connexin 43 / Q000235:genetics; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D017629:Gap Junctions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D025521:Tumor Suppressor Proteins
chemical_list: D033962:Adaptor Protein Complex 2; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002966:Clathrin; D018031:Connexin 43; C102885:DAB2 protein, human; D025521:Tumor Suppressor Proteins; D034281:Dynamins