Connexin43 phosphorylation by PKC and MAPK signals VEGF-mediated gap junction internalization

Molecular Biology of the Cell

Volumn 26, Issue 15, 2015, Pages 2755-2768

  Nimlamool, Wutigri ^a   Andrews, Rachael M Kells ^a   Falk, Matthias M ^a  

^a LEHIGH UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CONNEXIN 43; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN KINASE C; SERINE; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; GJA1 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE; VASCULOTROPIN A; VEGFA PROTEIN, HUMAN;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL COMMUNICATION; CELL CONTACT; CELL JUNCTION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOPLASM; ENDOCYTOSIS; GAP JUNCTION; INTERNALIZATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN INDUCTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSPORT VESICLE; UMBILICAL VEIN ENDOTHELIAL CELL; UPREGULATION; ANIMAL; CELL LINE; DRUG EFFECTS; HUMAN; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PIG;

SUS;

ANIMALS; CELL COMMUNICATION; CELL LINE; CONNEXIN 43; GAP JUNCTIONS; HUMANS; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; PHOSPHORYLATION; PROTEIN KINASE C; SWINE; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84938926820     PISSN: 10591524     EISSN: 19394586     Source Type: Journal    
DOI: 10.1091/mbc.E14-06-1105     Document Type: Article

References (74)

1. 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.
2. Beardslee MA, Laing JG, Beyer EC, Saffitz JE (1998). Rapid turnover of connexin43 in the adult rat heart. Circ Res 83, 629-635.
3. Berthoud VM, Minogue PJ, Laing JG, Beyer EC (2004). Pathways for degradation of connexins and gap junctions. Cardiovasc Res 62, 256-267.
4. Brock TA, Dvorak HF, Senger DR (1991). Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am J Pathol 138, 213-221.
5. Chang EH, Van Camp G, Smith RJ (2003). The role of connexins in human disease. Ear Hear 24, 314-323.
6. Cone AC, Cavin G, Ambrosi C, Hakozaki H, Wu-Zhang AX, Kunkel MT, Newton AC, Sosinsky GE (2014). Protein kinase cdelta-mediated phosphorylation of connexin43 gap junction channels causes movement within gap junctions followed by vesicle internalization and protein degradation. J Biol Chem 289, 8781-8798.
7. Cronier L, Crespin S, Strale PO, Defamie N, Mesnil M (2009). Gap junctions and cancer: new functions for an old story. Antioxid Redox Signal 11, 323-338.
8. de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT (1992). The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255, 989-991.
9. Dunn CA, Lampe PD (2014). Injury-triggered Akt phosphorylation of Cx43: a ZO-1-driven molecular switch that regulates gap junction size. J Cell Sci 127, 455-464.
10. Dutta D, Williamson CD, Cole NB, Donaldson JG (2012). Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis. PLoS One 7, e45799.
11. Falk MM (2000). Connexin-specific distribution within gap junctions revealed in living cells. J Cell Sci 113, 4109-4120.
12. 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.
13. Falk MM, Kells RM, Berthoud VM (2014). Degradation of connexins and gap junctions. FEBS Lett 588, 1221-1229.
14. Fallon RF, Goodenough DA (1981). Five-hour half-life of mouse liver gapjunction protein. J Cell Biol 90, 521-526.
15. Ferrara N (2004). Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25, 581-611.
16. Fong JT, Kells RM, Falk MM (2013). Two tyrosine-based sorting signals in the Cx43 C-terminus cooperate to mediate gap junction endocytosis. Mol Biol Cell 24, 2834-2848.
17. Fong JT, Nimlamool W, Falk MM (2014). EGF induces efficient Cx43 gap junction endocytosis in mouse embryonic stem cell colonies via phosphorylation of Ser262, Ser279/282, and Ser368. FEBS Lett 588, 836-844.
18. 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.
19. 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.
20. Gilleron J, Carette D, Fiorini C, Benkdane M, Segretain D, Pointis G (2009). Connexin 43 gap junction plaque endocytosis implies molecular remodelling of ZO-1 and c-Src partners. Commun Integr Biol 2, 104-106.
21. Gilleron J, Carette D, Fiorini C, Dompierre J, Macia E, Denizot JP, Segretain D, Pointis G (2011). The large GTPase dynamin2: a new player in connexin 43 gap junction endocytosis, recycling and degradation. Int J Biochem Cell Biol 43, 1208-1217.
22. Goodenough DA, Gilula NB (1974). The splitting of hepatocyte gap junctions and zonulae occludentes with hypertonic disaccharides. J Cell Biol 61, 575-590.
23. Goodenough DA, Goliger JA, Paul DL (1996). Connexins, connexons, and intercellular communication. Annu Rev Biochem 65, 475-502.
24. Gumpert AM, Varco JS, Baker SM, Piehl M, Falk MM (2008). Doublemembrane gap junction internalization requires the clathrin-mediated endocytic machinery. FEBS Lett 582, 2887-2892.
25. Guthrie SC, Gilula NB (1989). Gap junctional communication and development. Trends Neurosci 12, 12-16.
26. Hansen SH, Sandvig K, van Deurs B (1993). Clathrin and HA2 adaptors: effects of potassium depletion, hypertonic medium, and cytosol acidification. J Cell Biol 121, 61-72.
27. Heuser JE, Anderson RG (1989). Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. J Cell Biol 108, 389-400.
28. Huang XD, Horackova M, Pressler ML (1996). Changes in the expression and distribution of connexin 43 in isolated cultured adult guinea pig cardiomyocytes. Exp Cell Res 228, 254-261.
29. Johnson KE, Mitra S, Katoch P, Kelsey LS, Johnson KR, Mehta PP (2013). Phosphorylation on Ser-279 and Ser-282 of connexin43 regulates endocytosis and gap junction assembly in pancreatic cancer cells. Mol Biol Cell 24, 715-33.
30. 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.
31. Jordan K, Solan JL, Dominguez M, Sia M, Hand A, Lampe PD, Laird DW (1999). Trafficking, assembly, and function of a connexin43-green fluorescent protein chimera in live mammalian cells. Mol Biol Cell 10, 2033-2050.
32. Kanemitsu MY, Jiang W, Eckhart W (1998). Cdc2-mediated phosphorylation of the gap junction protein, connexin43, during mitosis. Cell Growth Differ 9, 13-21.
33. Kevil CG, Payne DK, Mire E, Alexander JS (1998). Vascular permeability factor/ vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins. J Biol Chem 273, 15099-15103.
34. Kroll J, Waltenberger J (1997). The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells. J Biol Chem 272, 32521-32527.
35. Kumar NM, Gilula NB (1996). The gap junction communication channel. Cell 84, 381-388.
36. Lampe PD, TenBroek EM, Burt JM, Kurata WE, Johnson RG, Lau AF (2000). Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication. J Cell Biol 149, 1503-1512.
37. 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.
38. 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.
39. Leithe E, Rivedal E (2004). Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43. J Cell Sci 117, 1211-1220.
40. Leithe E, Sirnes S, Omori Y, Rivedal E (2006). Downregulation of gap junctions in cancer cells. Crit Rev Oncog 12, 225-256.
41. Leykauf K, Durst M, Alonso A (2003). Phosphorylation and subcellular distribution of connexin43 in normal and stressed cells. Cell Tissue Res 311, 23-30.
42. Lin R, Warn-Cramer BJ, Kurata WE, Lau AF (2001). v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication. J Cell Biol 154, 815-827.
43. Loewenstein WR, Rose B (1992). The cell-cell channel in the control of growth. Semin Cell Biol 3, 59-79.
44. Luo T, Fredericksen BL, Hasumi K, Endo A, Garcia JV (2001). Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin. J Virol 75, 2488-2492.
45. Marcia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T (2006). Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell 10, 839-850.
46. Mehta PP, Bertram JS, Loewenstein WR (1986). Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44, 187-196.
47. Motley A, Bright NA, Seaman MN, Robinson MS (2003). Clathrin-mediated endocytosis in AP-2-depleted cells. J Cell Biol 162, 909-918.
48. Musil LS, Goodenough DA (1993). Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Cell 74, 1065-1077.
49. Naus CC, Hearn S, Zhu D, Nicholson BJ, Shivers RR (1993). Ultrastructural analysis of gap junctions in C6 glioma cells transfected with connexin43 cDNA. Exp Cell Res 206, 72-84.
50. Nickel B, Boller M, Schneider K, Shakespeare T, Gay V, Murray SA (2013). Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission. J Cell Sci 126, 2607-2616.
51. Nickel BM, DeFranco BH, Gay VL, Murray SA (2008). Clathrin and Cx43 gap junction plaque endoexocytosis. Biochem Biophys Res Commun 374, 679-682.
52. 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.
53. Petrich BG, Gong X, Lerner DL, Wang X, Brown JH, Saffitz JE, Wang Y (2002). c-Jun N-terminal kinase activation mediates downregulation of connexin43 in cardiomyocytes. Circ Res 91, 640-647.
54. 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.
55. Polontchouk L, Ebelt B, Jackels M, Dhein S (2002). Chronic effects of endothelin 1 and angiotensin II on gap junctions and intercellular communication in cardiac cells. FASEB J 16, 87-89.
56. 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.
57. Qi JH, Claesson-Welsh L (2001). VEGF-induced activation of phosphoinositide 3-kinase is dependent on focal adhesion kinase. Exp Cell Res 263, 173-182.
58. 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.
59. Simon AM (1999). Gap junctions: more roles and new structural data. Trends Cell Biol 9, 169-170.
60. Sirnes S, Kjenseth A, Leithe E, Rivedal E (2009). Interplay between PKC and the MAP kinase pathway in Connexin43 phosphorylation and inhibition of gap junction intercellular communication. Biochem Biophys Res Commun 382, 41-45.
61. Solan JL, Lampe PD (2007). Key connexin 43 phosphorylation events regulate the gap junction life cycle. J Membr Biol 217, 35-41.
62. Solan JL, Lampe PD (2014). Specific Cx43 phosphorylation events regulate gap junction turnover in vivo. FEBS Lett 588, 1423-1429.
63. Suarez S, Ballmer-Hofer K (2001). VEGF transiently disrupts gap junctional communication in endothelial cells. J Cell Sci 114, 1229-1235.
64. Su V, Lau AF (2014). Connexins: mechanisms regulating protein levels and intercellular communication. FEBS Lett 588, 1212-1220.
65. Sulkowski S, Sulkowska M, Skrzydlewska E (1999). Gap junctional intercellular communication and carcinogenesis. Pol J Pathol 50, 227-233.
66. Suzuma K, Naruse K, Suzuma I, Takahara N, Ueki K, Aiello LP, King GL (2000). Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells. J Biol Chem 275, 40725-40731.
67. Swenson KI, Piwnica-Worms H, McNamee H, Paul DL (1990). Tyrosine phosphorylation of the gap junction protein connexin43 is required for the pp60v-src-induced inhibition of communication. Cell Regul 1, 989-1002.
68. Takahashi T, Yamaguchi S, Chida K, Shibuya M (2001). A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 20, 2768-2778.
69. Thvenin AF, Kowal TJ, Fong JT, Kells RM, Fisher CG, Falk MM (2013). Proteins and mechanisms regulating gap junction assembly. internalization and degradation. Physiology 28, 93-116.
70. Thuringer D (2004). The vascular endothelial growth factor-induced disruption of gap junctions is relayed by an autocrine communication via ATP release in coronary capillary endothelium. Ann NY Acad Sci 1030, 14-27.
71. Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH (1994). Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem 269, 26988-26995.
72. Warn-Cramer BJ, Lampe PD, Kurata WE, Kanemitsu MY, Loo LW, Eckhart W, Lau AF (1996). Characterization of the mitogen-activated protein kinase phosphorylation sites on the connexin-43 gap junction protein. J Biol Chem 271, 3779-3786.
73. Warn-Cramer BJ, Lau AF (2004). Regulation of gap junctions by tyrosine protein kinases. Biochim Biophys Acta 1662, 81-95.
74. Wu X, Zhao X, Baylor L, Kaushal S, Eisenberg E, Greene LE (2001). Clathrin exchange during clathrin-mediated endocytosis. J Cell Biol 155, 291-300.