PMID- 25818265 OWN - NLM STAT- MEDLINE DCOM- 20160329 LR - 20161020 IS - 1768-322X (Electronic) IS - 0248-4900 (Linking) VI - 107 IP - 7 DP - 2015 Jul TI - New cellular mechanisms of gap junction degradation and recycling. PG - 218-31 LID - 10.1111/boc.201400048 [doi] AB - BACKGROUND INFORMATION: 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. CI - (c) 2015 Societe Francaise des Microscopies and Societe de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd. FAU - Carette, Diane AU - Carette D AD - INSERM U 1065, Team 5 <>, University of Nice Sophia-Antipolis, Nice cedex 3, 06204, France. AD - UMR S1147, University Paris Descartes, Paris, 75006, France. AD - University of Versailles, Saint Quentin, 78035, France. FAU - Gilleron, Jerome AU - Gilleron J AD - INSERM U 1065, Team 5 <>, University of Nice Sophia-Antipolis, Nice cedex 3, 06204, France. FAU - Denizot, Jean-Pierre AU - Denizot JP AD - Unite de Neurosciences, Information et Complexite, CNRS UPR3293, Gif-sur-Yvette, 91190, France. FAU - Grant, Kirsty AU - Grant K AD - Unite de Neurosciences, Information et Complexite, CNRS UPR3293, Gif-sur-Yvette, 91190, France. FAU - Pointis, Georges AU - Pointis G AD - INSERM U 1065, Team 5 <>, University of Nice Sophia-Antipolis, Nice cedex 3, 06204, France. FAU - Segretain, Dominique AU - Segretain D AD - UMR S1147, University Paris Descartes, Paris, 75006, France. AD - University of Versailles, Saint Quentin, 78035, France. LA - eng PT - Journal Article DEP - 20150506 PL - England TA - Biol Cell JT - Biology of the cell JID - 8108529 RN - 0 (Connexins) SB - IM MH - Autophagy/*physiology MH - Cell Membrane/genetics/*metabolism/ultrastructure MH - Connexins/genetics/*metabolism MH - Gap Junctions/genetics/*metabolism/ultrastructure MH - HeLa Cells MH - Humans MH - Lysosomes/genetics/*metabolism/ultrastructure MH - Microscopy, Electron, Transmission MH - Microscopy, Fluorescence MH - *Proteolysis OTO - NOTNLM OT - Autophagy OT - Connexin OT - Degradative processes OT - Endo-lysosomal pathway OT - Gap junction EDAT- 2015/03/31 06:00 MHDA- 2016/03/30 06:00 CRDT- 2015/03/31 06:00 PHST- 2014/06/17 00:00 [received] PHST- 2015/03/23 00:00 [accepted] PHST- 2015/03/31 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2016/03/30 06:00 [medline] AID - 10.1111/boc.201400048 [doi] PST - ppublish SO - Biol Cell. 2015 Jul;107(7):218-31. doi: 10.1111/boc.201400048. Epub 2015 May 6.