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Degradation of Endocytosed Gap Junctions by Autophagosomal and Endo-/lysosomal Pathways: A Perspective

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Abstract

Gap junctions (GJs) are composed of tens to many thousands of double-membrane spanning GJ channels that cluster together to form densely packed channel arrays (termed GJ plaques) in apposing plasma membranes of neighboring cells. In addition to providing direct intercellular communication (GJIC, their hallmark function), GJs, based on their characteristic double-membrane-spanning configuration, likely also significantly contribute to physical cell-to-cell adhesion. Clearly, modulation (up-/down-regulation) of GJIC and of physical cell-to-cell adhesion is as vitally important as the basic ability of GJ formation itself. Others and we have previously described that GJs can be removed from the plasma membrane via the internalization of entire GJ plaques (or portions thereof) in a cellular process that resembles clathrin-mediated endocytosis. GJ endocytosis results in the formation of double-membrane vesicles [termed annular gap junctions (AGJs) or connexosomes] in the cytoplasm of one of the coupled cells. Four recent independent studies, consistent with earlier ultrastructural analyses, demonstrate the degradation of endocytosed AGJ vesicles via autophagy. However, in TPA-treated cells others report degradation of AGJs via the endo-/lysosomal degradation pathway. Here we summarize evidence that supports the concept that autophagy serves as the cellular default pathway for the degradation of internalized GJs. Furthermore, we highlight and discuss structural criteria that seem required for an alternate degradation via the endo-/lysosomal pathway.

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Abbreviations

AGJ:

Annular gap junction

CME:

Clathrin mediated endocytosis

Cx:

Connexin

DAG:

Diacylglycerol

GFP:

Green fluorescent protein

GJ:

Gap junction

GJIC:

Gap junction mediated intercellular communication

LAMP:

Lysosomal associated membrane protein

LC3:

Microtubule-associated protein light chain 3

PAEC:

Pulmonary artery endothelial cell

PE:

Phosphatidyl-ethanolamine

PKC:

Protein kinase C

RNAi:

RNA interference

SQSTM1:

Sequestosome 1

SUMO:

Small Ub-like modifier

TPA:

12-O-tetradecanoylphorbol 13-acetate

Ub:

Ubiquitin

WGA:

Wheat germ agglutinin

YFP:

Yellow fluorescent protein

References

  • Baker SM, Kim N, Gumpert AM, Segretain D, Falk MM (2008) Acute internalization of gap junctions in vascular endothelial cells in response to inflammatory mediator-induced G-protein coupled receptor activation. FEBS Lett 582:4039–4046

    Article  PubMed  CAS  Google Scholar 

  • Baldwin AL, Thurston G (2001) Mechanics of endothelial cell architecture and vascular permeability. Crit Rev Biomed Eng 29:247–278

    Article  PubMed  CAS  Google Scholar 

  • Barriere H, Nemes C, Lechardeur D, Khan-Mohammad M, Fruh K, Lukacs GL (2006) Molecular basis of oligoubiquitin-dependent internalization of membrane proteins in Mammalian cells. Traffic 7:282–297

    Article  PubMed  CAS  Google Scholar 

  • Beardslee MA, Laing JG, Beyer EC, Saffitz JE (1998) Rapid turnover of connexin43 in the adult rat heart. Circ Res 83:629–635

    Article  PubMed  CAS  Google Scholar 

  • Bejarano E, Girao H, Yuste A, Patel B, Marques C, Spray DC, Pereira P, Cuervo AM (2012) Autophagy modulates dynamics of connexins at the plasma membrane in a ubiquitin-dependent manner. Mol Biol Cell 23:2156–2169

    Article  PubMed  CAS  Google Scholar 

  • Belouzard S, Rouille Y (2006) Ubiquitylation of leptin receptor OB-Ra regulates its clathrin-mediated endocytosis. EMBO J 25:932–942

    Article  PubMed  CAS  Google Scholar 

  • Berthoud VM, Minogue PJ, Laing JG, Beyer EC (2004) Pathways for degradation of connexins and gap junctions. Cardiovasc Res 62:256–267

    Article  PubMed  CAS  Google Scholar 

  • Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171:603–614

    Article  PubMed  Google Scholar 

  • Blomstrand F, Venance L, Siren AL, Ezan P, Hanse E, Glowinski J, Ehrenreich H, Giaume C (2004) Endothelins regulate astrocyte gap junctions in rat hippocampal slices. Eur J Neurosci 19:1005–1015

    Article  PubMed  CAS  Google Scholar 

  • Catarino S, Ramalho JS, Marques C, Pereira P, Girao H (2011) Ubiquitin-mediated internalization of connexin43 is independent of the canonical endocytic tyrosine-sorting signal. Biochem J 437:255–267

    Article  PubMed  CAS  Google Scholar 

  • Ciani B, Layfield R, Cavey JR, Sheppard PW, Searle MS (2003) Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget’s disease of bone. J Biol Chem 278:37409–37412

    Article  PubMed  CAS  Google Scholar 

  • Delmar M, Coombs W, Sorgen P, Duffy HS, Taffet SM (2004) Structural bases for the chemical regulation of connexin43 channels. Cardiovasc Res 62:268–275

    Article  PubMed  CAS  Google Scholar 

  • Falk MM (2010) Adherens junctions remain dynamic. BMC Biol 8:34

    Article  PubMed  Google Scholar 

  • Falk MM, Baker SM, Gumpert AM, Segretain D, Buckheit RW 3rd (2009) Gap junction turnover is achieved by the internalization of small endocytic double-membrane vesicles. Mol Biol Cell 20:3342–3352

    Article  PubMed  CAS  Google Scholar 

  • Fallon RF, Goodenough DA (1981) Five-hour half-life of mouse liver gap-junction protein. J Cell Biol 90:521–526

    Article  PubMed  CAS  Google Scholar 

  • Fong JT, Kells RM, Gumpert AM, Marzillier JY, Davidson MW, Falk MM (2012) Internalized gap junctions are degraded by autophagy. Autophagy 8:794–811

    Google Scholar 

  • Fushman D, Wilkinson KD (2011) Structure and recognition of polyubiquitin chains of different lengths and linkage. F1000 Biol Rep 3:26

    Article  PubMed  Google Scholar 

  • Fykerud TA, Kjenseth A, Schink KO, Sirnes S, Bruun J, Omori Y, Brech A, Rivedal E, Leithe E (2012) Smad ubiquitination regulatory factor-2 controls gap junction intercellular communication by modulating endocytosis and degradation of connexin43. J Cell Sci. doi:10.1242/j cs.093500

  • Gaietta G, Deerinck TJ, Adams SR, Bouwer J, Tour O, Laird DW, Sosinsky GE, Tsien RY, Ellisman MH (2002) Multicolor and electron microscopic imaging of connexin trafficking. Science 296:503–507

    Article  PubMed  CAS  Google Scholar 

  • Geetha T, Jiang J, Wooten MW (2005) Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. Mol Cell 20:301–312

    Article  PubMed  CAS  Google Scholar 

  • Ghoshroy S, Goodenough DA, Sosinsky GE (1995) Preparation, characterization, and structure of half gap junctional layers split with urea and EGTA. J Membr Biol 146:15–28

    PubMed  CAS  Google Scholar 

  • Giepmans BN, Moolenaar WH (1998) The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein. Curr Biol 8:931–934

    Article  PubMed  CAS  Google Scholar 

  • Gilleron J, Fiorini C, Carette D, Avondet C, Falk MM, Segretain D, Pointis G (2008) Molecular reorganization of Cx43, Zo-1 and Src complexes during the endocytosis of gap junction plaques in response to a non-genomic carcinogen. J Cell Sci 121:4069–4078

    Article  PubMed  CAS  Google Scholar 

  • Ginzberg RD, Gilula NB (1979) Modulation of cell junctions during differentiation of the chicken otocyst sensory epithelium. Dev Biol 68:110–129

    Article  PubMed  CAS  Google Scholar 

  • Girao H, Catarino S, Pereira P (2009) Eps15 interacts with ubiquitinated Cx43 and mediates its internalization. Exp Cell Res 315:3587–3597

    Article  PubMed  CAS  Google Scholar 

  • Goodenough DA, Gilula NB (1974) The splitting of hepatocyte gap junctions and zonulae occludentes with hypertonic disaccharides. J Cell Biol 61:575–590

    Article  PubMed  CAS  Google Scholar 

  • Gumpert AM, Varco JS, Baker SM, Piehl M, Falk MM (2008) Double-membrane gap junction internalization requires the clathrin-mediated endocytic machinery. FEBS Lett 582:2887–2892

    Article  PubMed  CAS  Google Scholar 

  • Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, Lippincott-Schwartz J (2010) Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141:656–667

    Article  PubMed  CAS  Google Scholar 

  • Hawryluk MJ, Keyel PA, Mishra SK, Watkins SC, Heuser JE, Traub LM (2006) Epsin 1 is a polyubiquitin-selective clathrin-associated sorting protein. Traffic 7:262–281

    Article  PubMed  CAS  Google Scholar 

  • Hesketh GG, Shah MH, Halperin VL, Cooke CA, Akar FG, Yen TE, Kass DA, Machamer CE, Van Eyk JE, Tomaselli GF (2010) Ultrastructure and regulation of lateralized connexin43 in the failing heart. Circ Res 106:1153–1163

    Article  PubMed  CAS  Google Scholar 

  • Hicke L (2001) Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol 2:195–201

    Article  PubMed  CAS  Google Scholar 

  • Hicke L, Dunn R (2003) Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol 19:141–172

    Article  PubMed  CAS  Google Scholar 

  • Hung SY, Huang WP, Liou HC, Fu WM (2009) Autophagy protects neuron from Abeta-induced cytotoxicity. Autophagy 5:502–510

    Article  PubMed  CAS  Google Scholar 

  • Hunter AW, Barker RJ, Zhu C, Gourdie RG (2005) Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell 16:5686–5698

    Article  PubMed  CAS  Google Scholar 

  • Jordan K, Chodock R, Hand AR, Laird DW (2001) The origin of annular junctions: a mechanism of gap junction internalization. J Cell Sci 114:763–773

    PubMed  CAS  Google Scholar 

  • Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728

    Article  PubMed  CAS  Google Scholar 

  • Kjenseth A, Fykerud T, Rivedal E, Leithe E (2010) Regulation of gap junction intercellular communication by the ubiquitin system. Cell Signal 22:1267–1273

    Article  PubMed  CAS  Google Scholar 

  • Kjenseth A, Fykerud TA, Sirnes S, Bruun J, Kolberg M, Yohannes Z, Omori Y, Rivedal E, Leithe E (2012) The gap junction channel protein connexin43 is covalently modified and regulated by SUMOylation. J Biol Chem 287:15851–15861

    Article  PubMed  CAS  Google Scholar 

  • Laing JG, Tadros PN, Westphale EM, Beyer EC (1997) Degradation of connexin43 gap junctions involves both the proteasome and the lysosome. Exp Cell Res 236:482–492

    Article  PubMed  CAS  Google Scholar 

  • Laird DW (2005) Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation. Biochim Biophys Acta 1711:172–182

    Article  PubMed  CAS  Google Scholar 

  • Lampe PD, Lau AF (2004) The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol 36:1171–1186

    Article  PubMed  CAS  Google Scholar 

  • Lane NJ, Swales LS (1980) Dispersal of junctional particles, not internalization, during the in vivo disappearance of gap junctions. Cell 19:579–586

    Article  PubMed  CAS  Google Scholar 

  • Larsen WJ, Tung HN, Murray SA, Swenson CA (1979) Evidence for the participation of actin microfilaments and bristle coats in the internalization of gap junction membrane. J Cell Biol 83:576–587

    Article  PubMed  CAS  Google Scholar 

  • Lauf U, Giepmans BN, Lopez P, Braconnot S, Chen SC, Falk MM (2002) Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells. Proc Natl Acad Sci USA 99:10446–10451

    Article  PubMed  CAS  Google Scholar 

  • Leach DH, Oliphant LW (1984) Degradation of annular gap junctions of the equine hoof wall. Acta Anat (Basel) 120:214–219

    Article  CAS  Google Scholar 

  • Leithe E, Rivedal E (2004a) Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43. J Cell Sci 117:1211–1220

    Article  PubMed  CAS  Google Scholar 

  • Leithe E, Rivedal E (2004b) Ubiquitination and down-regulation of gap junction protein connexin-43 in response to 12-O-tetradecanoylphorbol 13-acetate treatment. J Biol Chem 279:50089–50096

    Article  PubMed  CAS  Google Scholar 

  • Leithe E, Kjenseth A, Sirnes S, Stenmark H, Brech A, Rivedal E (2009) Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101. J Cell Sci 122:3883–3893

    Article  PubMed  CAS  Google Scholar 

  • Leithe E, Sirnes S, Fykerud T, Kjenseth A, Rivedal E (2011) Endocytosis and post-endocytic sorting of connexins. Biochim Biophys Acta 1818:1870–1879

    PubMed  Google Scholar 

  • Lichtenstein A, Minogue PJ, Beyer EC, Berthoud VM (2011) Autophagy: a pathway that contributes to connexin degradation. J Cell Sci 124:910–920

    Article  PubMed  CAS  Google Scholar 

  • Lum H, Malik AB (1994) Regulation of vascular endothelial barrier function. Am J Physiol 267:L223–L241

    PubMed  CAS  Google Scholar 

  • Madshus IH (2006) Ubiquitin binding in endocytosis—how tight should it be and where does it happen? Traffic 7:258–261

    Article  PubMed  CAS  Google Scholar 

  • Mari M, Tooze SA, Reggiori F (2011) The puzzling origin of the autophagosomal membrane. F1000 Biol Rep 3:25

    Article  PubMed  Google Scholar 

  • Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis NT, Izumi T, Noda T, Yoshimori T (2010) Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J Cell Biol 190:511–521

    Article  PubMed  CAS  Google Scholar 

  • Mazet F, Wittenberg BA, Spray DC (1985) Fate of intercellular junctions in isolated adult rat cardiac cells. Circ Res 56:195–204

    Article  PubMed  CAS  Google Scholar 

  • Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36:2491–2502

    Article  PubMed  CAS  Google Scholar 

  • Moreno AP (2005) Connexin phosphorylation as a regulatory event linked to channel gating. Biochim Biophys Acta 1711:164–171

    Article  PubMed  CAS  Google Scholar 

  • Musil LS, Le AC, VanSlyke JK, Roberts LM (2000) Regulation of connexin degradation as a mechanism to increase gap junction assembly and function. J Biol Chem 275:25207–25215

    Article  PubMed  CAS  Google Scholar 

  • Pahujaa M, Anikin M, Goldberg GS (2007) Phosphorylation of connexin43 induced by Src: regulation of gap junctional communication between transformed cells. Exp Cell Res 313:4083–4090

    Article  PubMed  CAS  Google Scholar 

  • Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282:24131–24145

    Article  PubMed  CAS  Google Scholar 

  • Pfeifer U (1980) Autophagic sequestration of internalized gap junctions in rat liver. Eur J Cell Biol 21:244–246

    PubMed  CAS  Google Scholar 

  • Piehl M, Lehmann C, Gumpert A, Denizot JP, Segretain D, Falk MM (2007) Internalization of large double-membrane intercellular vesicles by a clathrin-dependent endocytic process. Mol Biol Cell 18:337–347

    Article  PubMed  CAS  Google Scholar 

  • Pohl C, Jentsch S (2009) Midbody ring disposal by autophagy is a post-abscission event of cytokinesis. Nat Cell Biol 11:65–70

    Article  PubMed  CAS  Google Scholar 

  • Postma FR, Hengeveld T, Alblas J, Giepmans BN, Zondag GC, Jalink K, Moolenaar WH (1998) Acute loss of cell–cell communication caused by G protein-coupled receptors: a critical role for c-Src. J Cell Biol 140:1199–1209

    Article  PubMed  CAS  Google Scholar 

  • Qin H, Shao Q, Igdoura SA, Alaoui-Jamali MA, Laird DW (2003) Lysosomal and proteasomal degradation play distinct roles in the life cycle of Cx43 in gap junctional intercellular communication-deficient and -competent breast tumor cells. J Biol Chem 278:30005–30014

    Article  PubMed  CAS  Google Scholar 

  • Ravikumar B, Imarisio S, Sarkar S, O’Kane CJ, Rubinsztein DC (2008) Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J Cell Sci 121:1649–1660

    Article  PubMed  CAS  Google Scholar 

  • Ravikumar B, Moreau K, Jahreiss L, Puri C, Rubinsztein DC (2010) Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat Cell Biol 12:747–757

    Article  PubMed  CAS  Google Scholar 

  • Rhett JM, Gourdie RG (2011) The perinexus: a new feature of Cx43 gap junction organization. Heart Rhythm 9:619–623

    Article  PubMed  Google Scholar 

  • Rhett JM, Jourdan J, Gourdie RG (2011) Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1. Mol Biol Cell 22:1516–1528

    Article  PubMed  CAS  Google Scholar 

  • Schnell DJ, Hebert DN (2003) Protein translocons: multifunctional mediators of protein translocation across membranes. Cell 112:491–505

    Article  PubMed  CAS  Google Scholar 

  • Seibenhener ML, Babu JR, Geetha T, Wong HC, Krishna NR, Wooten MW (2004) Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24:8055–8068

    Article  PubMed  CAS  Google Scholar 

  • Severs NJ, Shovel KS, Slade AM, Powell T, Twist VW, Green CR (1989) Fate of gap junctions in isolated adult mammalian cardiomyocytes. Circ Res 65:22–42

    Article  PubMed  CAS  Google Scholar 

  • Shih SC, Katzmann DJ, Schnell JD, Sutanto M, Emr SD, Hicke L (2002) Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis. Nat Cell Biol 4:389–393

    Article  PubMed  CAS  Google Scholar 

  • Sigismund S, Woelk T, Puri C, Maspero E, Tacchetti C, Transidico P, Di Fiore PP, Polo S (2005) Clathrin-independent endocytosis of ubiquitinated cargos. Proc Natl Acad Sci USA 102:2760–2765

    Google Scholar 

  • Solan JL, Lampe PD (2009) Connexin43 phosphorylation: structural changes and biological effects. Biochem J 419:261–272

    Article  PubMed  CAS  Google Scholar 

  • Spinella F, Rosano L, Di Castro V, Nicotra MR, Natali PG, Bagnato A (2003) Endothelin-1 decreases gap junctional intercellular communication by inducing phosphorylation of connexin 43 in human ovarian carcinoma cells. J Biol Chem 278:41294–41301

    Article  PubMed  CAS  Google Scholar 

  • Stahl PD, Barbieri MA (2002) Multivesicular bodies and multivesicular endosomes: the “ins and outs” of endosomal traffic. Sci STKE 2002:pe32

  • Su V, Lau AF (2012) Ubiquitination, intracellular trafficking, and degradation of connexins. Arch Biochem Biophys 524:16–22

    Article  PubMed  CAS  Google Scholar 

  • Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M (1998) Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem 273:12725–12731

    Article  PubMed  CAS  Google Scholar 

  • van Zeijl L, Ponsioen B, Giepmans BN, Ariaens A, Postma FR, Varnai P, Balla T, Divecha N, Jalink K, Moolenaar WH (2007) Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. J Cell Biol 177:881–891

    Article  PubMed  Google Scholar 

  • Warn-Cramer BJ, Lau AF (2004) Regulation of gap junctions by tyrosine protein kinases. Biochim Biophys Acta 1662:81–95

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson CR, Seeger M, Hartmann-Petersen R, Stone M, Wallace M, Semple C, Gordon C (2001) Proteins containing the UBA domain are able to bind to multi-ubiquitin chains. Nat Cell Biol 3:939–943

    Article  PubMed  CAS  Google Scholar 

  • Wong CW, Christen T, Kwak BR (2004) Connexins in leukocytes: shuttling messages? Cardiovasc Res 62:357–367

    Article  PubMed  CAS  Google Scholar 

  • Wright CS (1984) Structural comparison of the two distinct sugar binding sites in wheat germ agglutinin isolectin II. J Mol Biol 178:91–104

    Article  PubMed  CAS  Google Scholar 

  • Yen WL, Shintani T, Nair U, Cao Y, Richardson BC, Li Z, Hughson FM, Baba M, Klionsky DJ (2010) The conserved oligomeric Golgi complex is involved in double-membrane vesicle formation during autophagy. J Cell Biol 188:101–114

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Work in the laboratory of M.M.F. is supported by NIHs NIGMS (grant GM55725) and by Lehigh University. We thank additional members of the Falk laboratory for critical comments. We wish to extend our sincere appreciation to Ross Johnson, whose dedication to gap junctions has revealed so many exciting aspects of this truly amazing cellular structure. His excitement and passion has fueled this research and will fuel the passion of many generations of researchers to come. Although we know so much about gap junctions, so much more still needs to be discovered! His contributions to this field have been significant.

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  1. Department of Biological Sciences, Lehigh University, 111 Research Drive, Iacocca Hall, D-218, Bethlehem, PA, 18015, USA

    Matthias M. Falk, John T. Fong, Rachael M. Kells, Michael C. O’Laughlin, Tia J. Kowal & Anastasia F. Thévenin

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  1. Matthias M. Falk
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  2. John T. Fong
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  3. Rachael M. Kells
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  4. Michael C. O’Laughlin
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  5. Tia J. Kowal
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  6. Anastasia F. Thévenin
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Correspondence to Matthias M. Falk.

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Falk, M.M., Fong, J.T., Kells, R.M. et al. Degradation of Endocytosed Gap Junctions by Autophagosomal and Endo-/lysosomal Pathways: A Perspective. J Membrane Biol 245, 465–476 (2012). https://doi.org/10.1007/s00232-012-9464-0

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