Connexin 46 (Cx46) gap junctions provide a pathway for the delivery of glutathione to the lens nucleus

Journal of Biological Chemistry

Volumn 289, Issue 47, 2014, Pages 32694-32702

  Slavi, Nefeli ^a   Rubinos, Clio ^a   Li, Leping ^b   Sellitto, Caterina ^b   White, Thomas W ^b   Mathias, Richard ^b   Srinivas, Miduturu ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

^b STONY BROOK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ELECTROPHYSIOLOGY; MICROCIRCULATION;

DIVALENT ANIONS; EXTRACELLULAR; GAP JUNCTION CHANNELS; GAP JUNCTIONS; GLUTATHIONE DISULFIDE; LENS PROTEINS; LENS TRANSPARENCY; SINGLE CHANNELS;

PEPTIDES;

CONNEXIN 43; CONNEXIN 46; CONNEXIN 50; GAP JUNCTION PROTEIN; GLUTATHIONE; UNCLASSIFIED DRUG; EYE PROTEIN; GLUTATHIONE DISULFIDE;

ADVECTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN CELL; CELL NUCLEUS; CELL SURFACE; CONTROLLED STUDY; GAP JUNCTION; HYDROSTATIC PRESSURE; LENS NUCLEUS; MICROCIRCULATION; MOLECULAR DOCKING; MOUSE; NONHUMAN; PROTEIN ANALYSIS; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ALGORITHM; ANIMAL; BIOLOGICAL MODEL; C57BL MOUSE; DIFFUSION; FEMALE; GENETICS; KNOCKOUT MOUSE; LENS; MEMBRANE POTENTIAL; METABOLISM; OOCYTE; PATCH CLAMP TECHNIQUE; PHYSIOLOGY; TRANSPORT AT THE CELLULAR LEVEL; TUMOR CELL LINE; XENOPUS;

ALGORITHMS; ANIMALS; BIOLOGICAL TRANSPORT; CELL LINE, TUMOR; CONNEXINS; DIFFUSION; EYE PROTEINS; FEMALE; GAP JUNCTIONS; GLUTATHIONE; GLUTATHIONE DISULFIDE; LENS, CRYSTALLINE; MEMBRANE POTENTIALS; MICE, INBRED C57BL; MICE, KNOCKOUT; MODELS, BIOLOGICAL; OOCYTES; PATCH-CLAMP TECHNIQUES; XENOPUS;

EID: 84911874671     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.597898     Document Type: Article

References (44)

1. Giblin, F. J. (2000) Glutathione: a vital lens antioxidant. J. Ocul. Pharmacol. Ther. 16, 121-135
2. Reddy, V. N. (1990) Glutathione and its function in the lens-an overview. Exp. Eye Res. 50, 771-778
3. Ganea, E., and Harding, J. J. (2006) Glutathione-related enzymes and the eye. Curr. Eye Res. 31, 1-11
4. Rathbun, W. B. (1984) Lenticular glutathione synthesis: rate-limiting factors in its regulation and decline. Curr. Eye Res. 3, 101-108
5. Lim, J., Li, L., Jacobs, M. D., Kistler, J., and Donaldson, P. J. (2007) Mapping of glutathione and its precursor amino acids reveals a role for GLYT2 in glycine uptake in the lens core. Invest. Ophthalmol. Vis. Sci. 48, 5142-5151
6. Lou, M. F. (2003) Redox regulation in the lens. Prog. Retin. Eye Res. 22, 657-682
7. Truscott, R. J. (2000) Age-related nuclear cataract: a lens transport problem. Ophthalmic Res. 32, 185-194
8. Bova, L. M., Sweeney, M. H., Jamie, J. F., and Truscott, R. J. (2001) Major changes in human ocular UVprotection with age. Invest. Ophthalmol. Vis. Sci. 42, 200-205
9. Dickerson, J. E., Jr., and Lou, M. F. (1993) A new mixed disulfide species in human cataractous and aged lenses. Biochim. Biophys. Acta 1157, 141-146
10. Harding, J. J. (1969) Glutathione-protein mixed disulphides in human lens. Biochem. J. 114, 88P-89P
11. Lou, M. F., and Dickerson, J. E., Jr. (1992) Protein-thiol mixed disulfides in human lens. Exp. Eye Res. 55, 889-896
12. Candia, O. A., Mathias, R., and Gerometta, R. (2012) Fluid circulation determined in the isolated bovine lens. Invest. Ophthalmol. Vis. Sci. 53, 7087-7096
13. Mathias, R. T., Kistler, J., and Donaldson, P. (2007) The lens circulation. J. Membr. Biol. 216, 1-16
14. Mathias, R. T., Rae, J. L., and Baldo, G. J. (1997) Physiological properties of the normal lens. Physiol. Rev. 77, 21-50
15. Baldo, G. J., and Mathias, R. T. (1992) Spatial variations in membrane properties in the intact rat lens. Biophys. J. 63, 518-529
16. Gao, J., Sun, X., Moore, L. C., White, T. W., Brink, P. R., and Mathias, R. T. (2011) Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling. J. Gen. Physiol. 137, 507-520
17. Donaldson, P. J., Musil, L. S., and Mathias, R. T. (2010) Point: A critical appraisal of the lens circulation model-an experimental paradigm for understanding the maintenance of lens transparency? Invest. Ophthalmol. Vis. Sci. 51, 2303-2306
18. Sweeney, M. H., Garland, D. L., and Truscott, R. J. (2003) Movement of cysteine in intact monkey lenses: the major site of entry is the germinative region. Exp. Eye Res. 77, 245-251
19. Sweeney, M. H., and Truscott, R. J. (1998) An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract. Exp. Eye Res. 67, 587-595
20. Gong, X., Baldo, G. J., Kumar, N. M., Gilula, N. B., and Mathias, R. T. (1998) Gap junctional coupling in lenses lacking α3 connexin. Proc. Natl. Acad. Sci. U.S.A. 95, 15303-15308
21. Paul, D. L., Ebihara, L., Takemoto, L. J., Swenson, K. I., and Goodenough, D. A. (1991) Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes. J. Cell Biol. 115, 1077-1089
22. White, T. W., Bruzzone, R., Goodenough, D. A., and Paul, D. L. (1992) Mouse Cx50, a functional member of the connexin family of gap junction proteins, is the lens fiber protein MP70. Mol. Biol. Cell 3, 711-720
23. White, T. W., Goodenough, D. A., and Paul, D. L. (1998) Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts. J. Cell Biol. 143, 815-825
24. Baldo, G. J., Gong, X., Martinez-Wittinghan, F. J., Kumar, N. M., Gilula, N. B., and Mathias, R. T. (2001) Gap junctional coupling in lenses from α(8) connexin knockout mice. J. Gen. Physiol. 118, 447-456
25. Martinez-Wittinghan, F. J., Sellitto, C., Li, L., Gong, X., Brink, P. R., Mathias, R. T., and White, T. W. (2003) Dominant cataracts result from incongruous mixing of wild-type lens connexins. J. Cell Biol. 161, 969-978
26. Martinez-Wittinghan, F. J., Sellitto, C., White, T. W., Mathias, R. T., Paul, D., and Goodenough, D. A. (2004) Lens gap junctional coupling is modulated by connexin identity and the locus of gene expression. Invest. Ophthalmol. Vis. Sci. 45, 3629-3637
27. Srinivas, M., Kronengold, J., Bukauskas, F. F., Bargiello, T. A., and Verselis, V. K. (2005) Correlative studies of gating in Cx46 and Cx50 hemichannels and gap junction channels. Biophys. J. 88, 1725-1739
28. Gong, X., Li, E., Klier, G., Huang, Q., Wu, Y., Lei, H., Kumar, N. M., Horwitz, J., and Gilula, N. B. (1997) Disruption of α3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91, 833-843
29. Gong, X., Agopian, K., Kumar, N. M., and Gilula, N. B. (1999) Genetic factors influence cataract formation in α3 connexin knockout mice. Dev. Genet. 24, 27-32
30. Srinivas, M., Costa, M., Gao, Y., Fort, A., Fishman, G. I., and Spray, D. C. (1999) Voltage dependence of macroscopic and unitary currents of gap junction channels formed by mouse connexin50 expressed in rat neuroblastoma cells. J. Physiol. 517, 673-689
31. Wang, H. Z., and Veenstra, R. D. (1997) Monovalent ion selectivity sequences of the rat connexin43 gap junction channel. J. Gen. Physiol. 109, 491-507
32. Trexler, E. B., Bukauskas, F. F., Kronengold, J., Bargiello, T. A., and Verselis, V. K. (2000) The first extracellular loop domain is a major determinant of charge selectivity in connexin46 channels. Biophys. J. 79, 3036-3051
33. Goldberg, G. S., Lampe, P. D., and Nicholson, B. J. (1999) Selective transfer of endogenous metabolites through gap junctions composed of different connexins. Nat. Cell Biol. 1, 457-459
34. Kannan, R., Yi, J. R., Tang, D., Zlokovic, B. V., and Kaplowitz, N. (1996) Identification of a novel, sodium-dependent, reduced glutathione transporter in the rat lens epithelium. Invest. Ophthalmol. Vis. Sci. 37, 2269-2275
35. Kannan, R., Yi, J. R., Zlokovic, B. V., and Kaplowitz, N. (1995) Molecular characterization of a reduced glutathione transporter in the lens. Invest. Ophthalmol. Vis. Sci. 36, 1785-1792
36. Maeda, S., Nakagawa, S., Suga, M., Yamashita, E., Oshima, A., Fujiyoshi, Y., and Tsukihara, T. (2009) Structure of the connexin 26 gap junction channel at 3.5 A˚ resolution. Nature 458, 597-602
37. Harris, A. L. (2001) Emerging issues of connexin channels: biophysics fills the gap. Q. Rev. Biophys. 34, 325-472
38. Harris, A. L. (2007) Connexin channel permeability to cytoplasmic molecules. Prog. Biophys. Mol. Biol. 94, 120-143
39. Shestopalov, V. I., and Bassnett, S. (2003) Development of a macromolecular diffusion pathway in the lens. J. Cell Sci. 116, 4191-4199
40. Shi, Y., Barton, K., De Maria, A., Petrash, J. M., Shiels, A., and Bassnett, S. (2009) The stratified syncytium of the vertebrate lens. J. Cell Sci. 122, 1607-1615
41. Shi, Y., De Maria, A. B., Wang, H., Mathias, R. T., FitzGerald, P. G., and Bassnett, S. (2011) Further analysis of the lens phenotype in Lim2-deficient mice. Invest. Ophthalmol. Vis. Sci. 52, 7332-7339
42. Truscott, R. J., and Augusteyn, R. C. (1977) The state of sulfhydryl groups in normal and cataractous human lenses. Exp. Eye Res. 25, 139-148
43. Gao, J., Wang, H., Sun, X., Varadaraj, K., Li, L., White, T. W., and Mathias, R. T. (2013) The effects of age on lens transport. Invest. Ophthalmol. Vis. Sci. 54, 7174-7187
44. Wang, Z., and Schey, K. L. (2009) Phosphorylation and truncation sites of bovine lens connexin 46 and connexin 50. Exp. Eye Res. 89, 898-904