title: New cellular mechanisms of gap junction degradation and recycling.
abstract: BACKGROUND
  Connexins (Cxs), the constitutive proteins of gap junctions, are key actors of many physiological processes. Therefore, alterations of Cx expression and degradation lead to the development of physiopathological disorders. Because of the formation of a double membrane vesicle termed annular gap junction (AGJ), gap junction degradation is a unique physiological process for which many cellular aspects remain unclear.
  
  
  RESULTS
  By using a combination of time-lapse fluorescence microscopy and high-resolution transmission electron microscopy, we evidenced new specific cellular events concerning gap junction degradation and recycling. Indeed, by time lapse video microscopy we demonstrated, for the first time to our knowledge, that an entire AGJ can be fully recycled back to the plasma membrane. Moreover, we dissected the degradative processes of gap junction by electron microscopy approaches. Interestingly, in addition to canonical autophagy and heterophagy pathways, previously described, we discovered that both pathways could sometimes intermingle. Strikingly, our results also highlighted a new lysosome-based autophagy pathway that could play a pivotal role in common autophagy degradation.
  
  
  CONCLUSIONS
  The present investigation reveals that AGJ degradation is a more complex process that it was previously thought. First, a complete recycling of the gap junction plaque after its internalisation could occur. Second, the degradation of this peculiar double membrane structure is possible through autophagy, heterophagy, hetero-autophagy or by lysosomal-based autophagy. Altogether, this work underlines novel aspects of gap junction degradation that could be extended to other cell biology processes.
authors.affiliation: INSERM U 1065, Team 5 «Physiopathological control of germ cell proliferation: genomic and non-genomic mechanisms», University of Nice Sophia-Antipolis, Nice cedex 3, 06204, France.|UMR S1147, University Paris Descartes, Paris, 75006, France.|University of Versailles, Saint Quentin, 78035, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Carette
authors.affiliation: INSERM U 1065, Team 5 «Physiopathological control of germ cell proliferation: genomic and non-genomic mechanisms», University of Nice Sophia-Antipolis, Nice cedex 3, 06204, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gilleron
authors.affiliation: Unité de Neurosciences, Information et Complexité, CNRS UPR3293, Gif-sur-Yvette, 91190, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Denizot
authors.affiliation: Unité de Neurosciences, Information et Complexité, CNRS UPR3293, Gif-sur-Yvette, 91190, France.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Grant
authors.affiliation: INSERM U 1065, Team 5 «Physiopathological control of germ cell proliferation: genomic and non-genomic mechanisms», University of Nice Sophia-Antipolis, Nice cedex 3, 06204, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Pointis
authors.affiliation: UMR S1147, University Paris Descartes, Paris, 75006, France.|University of Versailles, Saint Quentin, 78035, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Segretain
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D059748:Proteolysis
chemical_list: D017630:Connexins
keywords: Autophagy; Connexin; Degradative processes; Endo-lysosomal pathway; Gap junction