The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes

Frontiers in Cellular Neuroscience

Volumn 8, Issue OCT, 2014, Pages

  Abudara, Verónica ^a,e   Bechberger, John ^b   Freitas Andrade, Moises ^b   De Bock, Marijke ^c   Wang, Nan ^c   Bultynck, Geert ^d   Naus, Christian C ^b   Leybaert, Luc ^c   Giaume, Christian ^a  

^a PSL RESEARCH UNIVERSITY   (France)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c GHENT UNIVERSITY   (Belgium)

^d LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

^e UNIVERSIDAD DE LA REPÚBLICA   (Uruguay)

Author keywords

Astroglia; Connexins; Gap junctions; Glial cells; Mimetic peptide

Indexed keywords

CARBENOXOLONE; CONNEXIN 43; HELIOMYCIN; TRANSACTIVATOR PROTEIN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BRAIN; CELL COMMUNICATION; CELL CULTURE; CELL INTERACTION; GAP JUNCTION; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MOUSE; NERVE CELL; NEWBORN; NONHUMAN; PARENCHYMA;

EID: 84908255566     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00306     Document Type: Article

References (51)

1. Chever, O., Lee, C. Y., and Rouach, N. (2014). Astroglial connexin43 hemichannels tune Basal excitatory synaptic transmission. J. Neurosci. 34, 11228-11232. doi: 10.1523/JNEUROSCI.0015-14.2014
2. Cina, C., Maass, K., Theis, M., Willecke, K., Bechberger, J. F., and Naus, C. C. (2009). Involvement of the cytoplasmic C-terminal domain of connexin43 in neuronal migration. J. Neurosci. 29, 2009-2021. doi: 10.1523/JNEUROSCI.5025-08.2009
3. D'hondt, C., Iyyathurai, J., Wang, N., Gourdie, R. G., Himpens, B., Leybaert, L., et al. (2013). Negatively charged residues (Asp378 and Asp379) in the last ten amino acids of the C-terminal tail of Cx43 hemichannels are essential for loop/tail interactions. Biochem. Biophys. Res. Commun. 432, 707-712. doi: 10.1016/j.bbrc.2013.01.066
4. De Bock, M., Wang, N., Decrock, E., Bol, M., Gadicherla, A. K., Culot, M., et al. (2013). Endothelial calcium dynamics, connexin channels and blood-brain barrier function. Prog. Neurobiol. 108, 1-20. doi: 10.1016/j.pneurobio.2013.06.001
5. De Vuyst, E., Wang, N., Decrock, E., De Bock, M., Vinken, M., Van Moorhem, M., et al. (2009). Ca(2+) regulation of connexin 43 hemichannels in C6 glioma and glial cells. Cell Calcium 46, 176-187. doi: 10.1016/j.ceca.2009.07.002
6. Decrock, E., De Vuyst, E., Vinken, M., Van Moorhem, M., Vranckx, K., Wang, N., et al. (2009). Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model. Cell Death Differ. 16, 151-163. doi: 10.1038/cdd.2008.138
7. Elias, L. A., Wang, D. D., and Kriegstein, A. R. (2007). Gap junction adhesion is necessary for radial migration in the neocortex. Nature 448, 901-907. doi: 10.1038/nature06063
8. Evans, W. H., and Boitano, S. (2001). Connexin mimetic peptides: specific inhibitors of gap-junctional intercellular communication. Biochem. Soc. Trans. 29, 606-612. doi: 10.1042/BST0290606
9. Evans, W. H., De Vuyst, E., and Leybaert, L. (2006). The gap junction cellular internet: connexin hemichannels enter the signalling limelight. Biochem. J. 397, 1-14. doi: 10.1042/BJ20060175
10. Evans, W. H., and Leybaert, L. (2007). Mimetic peptides as blockers of connexin channel-facilitated intercellular communication. Cell Commun. Adhes. 14, 265-273. doi: 10.1080/15419060801891034
11. Ezan, P., Andre, P., Cisternino, S., Saubamea, B., Boulay, A. C., Doutremer, S., et al. (2012). Deletion of astroglial connexins weakens the blood-brain barrier. J. Cereb. Blood Flow Metab. 32, 1457-1467. doi: 10.1038/jcbfm.2012.45
12. Froger, N., Orellana, J. A., Calvo, C. F., Amigou, E., Kozoriz, M. G., Naus, C. C., et al. (2010). Inhibition of cytokine-induced connexin43 hemichannel activity in astrocytes is neuroprotective. Mol. Cell. Neurosci. 45, 37-46. doi: 10.1016/j.mcn.2010.05.007
13. Giaume, C., Fromaget, C., El Aoumari, A., Cordier, J., Glowinski, J., and Gros, D. (1991a). Gap junctions in cultured astrocytes: single-channel currents and characterization of channel-forming protein. Neuron 6, 133-143. doi: 10.1016/0896-6273(91)90128-M
14. Giaume, C., Koulakoff, A., Roux, L., Holcman, D., and Rouach, N. (2010). Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat. Rev. Neurosci. 11, 87-99. doi: 10.1038/nrn2757
15. Giaume, C., Leybaert, L., Naus, C. C., and Saez, J. C. (2013). Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles. Front. Pharmacol. 4:88. doi: 10.3389/fphar.2013.00088
16. Giaume, C., Marin, P., Cordier, J., Glowinski, J., and Premont, J. (1991b). Adrenergic regulation of intercellular communications between cultured striatal astrocytes from the mouse. Proc. Natl. Acad. Sci. U.S.A. 88, 5577-5581. doi: 10.1073/pnas.88.13.5577
17. Giaume, C., Orellana, J. A., Abudara, V., and Saez, J. C. (2012). Connexin-based channels in astrocytes: how to study their properties. Methods Mol. Biol. 814, 283-303. doi: 10.1007/978-1-61779-452-0_19
18. Giaume, C., and Theis, M. (2010). Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system. Brain Res. Rev. 63, 160-176. doi: 10.1016/j.brainresrev.2009.11.005
19. Harris, A. L. (2001). Emerging issues of connexin channels: biophysics fills the gap. Q. Rev. Biophys. 34, 325-472. doi: 10.1017/S0033583501003705
20. Houades, V., Rouach, N., Ezan, P., Kirchhoff, F., Koulakoff, A., and Giaume, C. (2006). Shapes of astrocyte networks in the juvenile brain. Neuron Glia Biol. 2, 3-14. doi: 10.1017/S1740925X06000081
21. Iyyathurai, J., D'hondt, C., Wang, N., De Bock, M., Himpens, B., Retamal, M. A., et al. (2013). Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: gap junctions versus hemichannels. Neuropharmacology 75, 491-505. doi: 10.1016/j.neuropharm.2013.04.050
22. Kozoriz, M. G., Bechberger, J. F., Bechberger, G. R., Suen, M. W., Moreno, A. P., Maass, K., et al. (2010). The connexin43 C-terminal region mediates neuroprotection during stroke. J. Neuropathol. Exp. Neurol. 69, 196-206. doi: 10.1097/NEN.0b013e3181cd44df
23. Koulakoff, A., Ezan, P., and Giaume, C. (2008). Neurons control the expression of connexin 30 and connexin 43 in mouse cortical astrocytes. Glia 56, 1299-1311. doi: 10.1002/glia.20698
24. Kunzelmann, P., Schroder, W., Traub, O., Steinhauser, C., Dermietzel, R., and Willecke, K. (1999). Late onset and increasing expression of the gap junction protein connexin30 in adult murine brain and long-term cultured astrocytes. Glia 25, 111-119.
25. Lutz, S. E., Zhao, Y., Gulinello, M., Lee, S. C., Raine, C. S., and Brosnan, C. F. (2009). Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. J. Neurosci. 29, 7743-7752. doi: 10.1523/JNEUROSCI.0341-09.2009
26. Meme, W., Calvo, C. F., Froger, N., Ezan, P., Amigou, E., Koulakoff, A., et al. (2006). Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by beta-amyloid. FASEB J. 20, 494-496. doi: 10.1096/fj.05-4297fje
27. Nakase, T., Söhl, G., Theis, M., Willecke, K., and Naus, C. C. (2004). Increased apoptosis and inflammation after focal brain ischemia in mice lacking connexin43 in astrocytes. Am. J. Pathol. 164, 2067-2075. doi: 10.1016/S0002-9440(10)63765-0
28. Nolte, C., Matyash, M., Pivneva, T., Schipke, C. G., Ohlemeyer, C., Hanisch, U. K., et al. (2001). GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia 33, 72-86. doi: 10.1002/1098-1136(20010101)33:1<72::AID-GLIA1007>3.0.CO;2-A
29. O'carroll, S. J., Alkadhi, M., Nicholson, L. F., and Green, C. R. (2008). Connexin 43 mimetic peptides reduce swelling, astrogliosis, and neuronal cell death after spinal cord injury. Cell Commun. Adhes. 15, 27-42. doi: 10.1080/15419060802014164
30. Omasits, U., Ahrens, C. H., Muller, S., and Wollscheid, B. (2014). Protter: interactive protein feature visualization and integration with experimental proteomic data. Bioinformatics 30, 884-886. doi: 10.1093/bioinformatics/btt607
31. Orellana, J. A., Shoji, K. F., Abudara, V., Ezan, P., Amigou, E., Saez, P. J., et al. (2011). Amyloid beta-induced death in neurons involves glial and neuronal hemichannels. J. Neurosci. 31, 4962-4977. doi: 10.1523/JNEUROSCI.6417-10.2011
32. Ozog, M. A., Siushansian, R., and Naus, C. C. (2002). Blocked gap junctional coupling increases glutamate-induced neurotoxicity in neuron-astrocyte co-cultures. J. Neuropathol. Exp. Neurol. 61, 132-141.
33. Pannasch, U., Freche, D., Dallerac, G., Ghezali, G., Escartin, C., Ezan, P., et al. (2014). Connexin 30 sets synaptic strength by controlling astroglial synapse invasion. Nat. Neurosci. 17, 549-558. doi: 10.1038/nn.3662
34. Pannasch, U., Vargova, L., Reingruber, J., Ezan, P., Holcman, D., Giaume, C., et al. (2011). Astroglial networks scale synaptic activity and plasticity. Proc. Natl. Acad. Sci. U.S.A. 108, 8467-8472. doi: 10.1073/pnas.1016650108
35. Ponsaerts, R., De Vuyst, E., Retamal, M., D'hondt, C., Vermeire, D., Wang, N., et al. (2010). Intramolecular loop/tail interactions are essential for connexin 43-hemichannel activity. FASEB J. 24, 4378-4395. doi: 10.1096/fj.09-153007
36. Ransom, B., and Giaume, C. (2013). "Gap junctions, hemichannels," in Neuroglia, eds H. Kettenmann and B. R. Ransom (New York, NY: Oxford University press), 292-305.
37. Retamal, M. A., Froger, N., Palacios-Prado, N., Ezan, P., Saez, P. J., Saez, J. C., et al. (2007). Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia. J. Neurosci. 27, 13781-13792. doi: 10.1523/JNEUROSCI.2042-07.2007
38. Riquelme, M. A., Kar, R., Gu, S., and Jiang, J. X. (2013). Antibodies targeting extracellular domain of connexins for studies of hemichannels. Neuropharmacology 75, 594-603. doi: 10.1016/j.neuropharm.2013.03.022
39. Rouach, N., Koulakoff, A., Abudara, V., Willecke, K., and Giaume, C. (2008). Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322, 1551-1555. doi: 10.1126/science.1164022
40. Roux, L., Benchenane, K., Rothstein, J. D., Bonvento, G., and Giaume, C. (2011). Plasticity of astroglial networks in olfactory glomeruli. Proc. Natl. Acad. Sci. U.S.A. 108, 18442-18446. doi: 10.1073/pnas.1107386108
41. Saez, J. C., and Leybaert, L. (2014). Hunting for connexin hemichannels. FEBS Lett. 588, 1205-1211. doi: 10.1016/j.febslet.2014.03.004
42. Spray, D. C., Ye, Z. C., and Ransom, B. R. (2006). Functional connexin "hemichannels": a critical appraisal. Glia 54, 758-773. doi: 10.1002/glia.20429
43. Stehberg, J., Moraga-Amaro, R., Salazar, C., Becerra, A., Echeverria, C., Orellana, J. A., et al. (2012). Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala. FASEB J. 26, 3649-3657. doi: 10.1096/fj.11-198416
44. Stout, C. E., Costantin, J. L., Naus, C. C., and Charles, A. C. (2002). Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J. Biol. Chem. 277, 10482-10488. doi: 10.1074/jbc.M109902200
45. Takeuchi, H., Mizoguchi, H., Doi, Y., Jin, S., Noda, M., Liang, J., et al. (2011). Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease. PLoS ONE 6:e21108. doi: 10.1371/journal.pone.0021108
46. Wallraff, A., Kohling, R., Heinemann, U., Theis, M., Willecke, K., and Steinhauser, C. (2006). The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J. Neurosci. 26, 5438-5447. doi: 10.1523/JNEUROSCI.0037-06.2006
47. Wang, N., De Bock, M., Antoons, G., Gadicherla, A. K., Bol, M., Decrock, E., et al. (2012). Connexin mimetic peptides inhibit Cx43 hemichannel opening triggered by voltage and intracellular Ca2+-elevation. Basic Res. Cardiol. 107, 304. doi: 10.1007/s00395-012-0304-2
48. Wang, N., De Bock, M., Decrock, E., Bol, M., Gadicherla, A., Bultynck, G., et al. (2013a). Connexin targeting peptides as inhibitors of voltage- and intracellular Ca2+-triggered Cx43 hemichannel opening. Neuropharmacology 75, 506-516. doi: 10.1016/j.neuropharm.2013.08.021
49. Wang, N., De Vuyst, E., Ponsaerts, R., Boengler, K., Palacios-Prado, N., Wauman, J., et al. (2013b). Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res. Cardiol. 108, 309. doi: 10.1007/s00395-012-0309-x
50. Warner, A., Clements, D. K., Parikh, S., Evans, W. H., and Dehaan, R. L. (1995). Specific motifs in the external loops of connexin proteins can determine gap junction formation between chick heart myocytes. J. Physiol. 488 (Pt 3), 721-728.
51. Ye, Z. C., Wyeth, M. S., Baltan-Tekkok, S., and Ransom, B. R. (2003). Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J. Neurosci. 23, 3588-3596.