Hostname: page-component-76fb5796d-qxdb6 Total loading time: 0 Render date: 2024-04-26T10:07:24.962Z Has data issue: false hasContentIssue false
  • English
  • Français

Quantitative immuno-electron microscopic analysis of nuclear respiratory factor 2 alpha and beta subunits: Normal distribution and activity-dependent regulation in mammalian visual cortex

Published online by Cambridge University Press:  05 April 2005

MARGARET T.T. WONG-RILEY ,
SHOU JING YANG ,
HUAN LING LIANG ,
GANG NING,  and
PAULETTE JACOBS
MARGARET T.T. WONG-RILEY
Affiliation:
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee
SHOU JING YANG
Affiliation:
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee Department of Pathology, 4th Military Medical University, Xi'an 710032, People's Republic of China
HUAN LING LIANG
Affiliation:
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee
GANG NING,
Affiliation:
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee Present address: Director, Electron Microscopy Facility, Huck Institute for Life Sciences, The Pennsylvania State University, 1 South Frear Lab, University Park, PA 16802, USA
PAULETTE JACOBS
Affiliation:
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee
Get access Rights & Permissions [Opens in a new window]

Abstract

The macaque visual cortex is exquisitely organized into columns, modules, and streams, much of which can be correlated with its metabolic organization revealed by cytochrome oxidase (CO). Plasticity in the adult primate visual system has also been documented by changes in CO activity. Yet, the molecular mechanism of regulating this enzyme remains not well understood. Being one of only four bigenomic enzymes in mammalian cells, the transcriptional regulation of this enzyme necessitates a potential bigenomic coordinator. Nuclear respiratory factor 2 (NRF-2) or GA-binding protein is a transcription factor that may serve such a critical role. The goal of the present study was to determine if the two major subunits of NRF-2, 2α and 2β, had distinct subcellular distribution in neurons of the rat and monkey visual cortex, if major metabolic neuronal types in the macaque exhibited different levels of the two subunits, and if they would respond differently to monocular impulse blockade. Quantitative immuno-electron microscopy was used. In both rats and monkeys, nuclear labeling of α and β subunits was mainly over euchromatin rather than heterochromatin, consistent with their active participation in transcriptional activity. Cytoplasmic labeling was over free ribosomes, the Golgi apparatus, and occasionally the nuclear envelope, signifying sites of synthesis and possible posttranslational modifications. The density of both subunits was much higher in the nucleus than in the cytoplasm for all neurons examined, again indicating that their major sites of cellular action is in the nucleus. In both layer IVC and supragranular puffs of the macaque visual cortex, the expression of both NRF-2α and β was higher in medium-sized, non-pyramidal (type C and C-like) cells previously shown to have higher CO activity than small, type A and A-like cells with low CO activity. Pyramidal, type B cells in puffs had intermediate levels of CO as well as NRF-2α and β labeling. Monocular impulse blockade induced a greater reduction of NRF-2 labeling in type C/C-like than type A/A-like cells. These results substantiate and extend our previous findings that NRF-2 is constitutively active in adult primate and rat visual cortical neurons, that it is expressed more strongly in metabolically more active neurons, and that its level is directly regulated by neuronal activity, the blockade of which imposes a greater down-regulation of this transcription factor in metabolically more active than less active neurons.

Keywords

Cytochrome oxidaseElectron-microscopic immunocytochemistryGA-binding proteinMonkey visual cortexRat visual cortexTranscription factor
Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 1 , January 2005 , pp. 1 - 18
Copyright
© 2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Attardi, G. & Schatz, G. (1988). Biogenesis of mitochondria. Annual Review of Cell Biology 4, 289–333.Google Scholar
Au, H.C. & Scheffler, I.E. (1998). Promoter analysis of the human succinate dehydrogenase iron-protein gene—both nuclear respiratory factors NRF-1 and NRF-2 are required. European Journal of Biochemistry 251, 164–174.Google Scholar
Banks, P., Mangnall, D., & Mayor, D. (1969). The re-distribution of cytochrome oxidase, noradrenaline and adenosine triphosphate in adrenergic nerves constricted at two points. Journal of Physiology 200, 745–762.Google Scholar
Batchelor, A.H., Piper, D.E., de la Brousse, F.C., McKnight, S.L., & Wolberger, C. (1998). The structure of GABPalpha/beta: An ETS domain-ankyrin repeat heterodimer bound to DNA. Science 279, 1037–1041.Google Scholar
Bulleit, R.F., Cui, H., Wang, J., & Lin, X. (1994). NMDA receptor activation in differentiating cerebellar cell cultures regulates the expression of a new POU gene, Cns-1. Journal of Neuroscience 14, 1584–1595.Google Scholar
Carder, R.K. & Hendry, S.H. (1994). Neuronal characterization, compartmental distribution, and activity-dependent regulation of glutamate immunoreactivity in adult monkey striate cortex. Journal of Neuroscience 14, 242–262.Google Scholar
Carter, R.S. & Avadhani, N.G. (1994). Cooperative binding of GA-binding protein transcription factors to duplicated transcription initiation region repeats of the cytochrome c oxidase subunit IV gene. Journal of Biological Chemistry 269, 4381–4387.Google Scholar
Chaudhuri, A., Matsubara, J.A., & Cynader, M.S. (1995). Neuronal activity in primate visual cortex assessed by immunostaining for the transcription factor Zif268. Visual Neuroscience 12, 35–50.CrossRefGoogle Scholar
Chinenov, Y., Schmidt, T., Yang, X.Y., & Martin, M.E. (1998). Identification of redox-sensitive cysteines in GA-binding protein-alpha that regulate DNA binding and heterodimerization. Journal of Biological Chemistry 273, 6203–6209.CrossRefGoogle Scholar
DeYoe, E.A. & Van Essen, D.C. (1988). Concurrent processing streams in monkey visual cortex. Trends in Neuroscience 11, 219–226.CrossRefGoogle Scholar
DeYoe, E.A., Trusk, T.C., & Wong-Riley, M.T. (1995). Activity correlates of cytochrome oxidase-defined compartments in granular and supragranular layers of primary visual cortex of the macaque monkey. Visual Neuroscience 12, 629–639.CrossRefGoogle Scholar
Erecinska, M. & Silver, I.A. (1989). ATP and brain function. Journal of Cerebral Blood Flow and Metabolism 9, 2–19.CrossRefGoogle Scholar
Fisher, R.P. & Clayton, D.A. (1988). Purification and characterization of human mitochondrial transcription factor 1. Molecular and Cellular Biology 8, 3496–3509.CrossRefGoogle Scholar
Flory, E., Hoffmeyer, A., Smola, U., Rapp, U.R., & Bruder, J.T. (1996). Raf-1 kinase targets GA-binding protein in transcriptional regulation of the human immunodeficiency virus type 1 promoter. Journal of Virology 70, 2260–2268.Google Scholar
Frenster, J.H. (1972). Ultrastructural probes of chromatin within living human lymphocytes. Nature: New Biology 236, 175–176.Google Scholar
Fromm, L. & Burden, S.J. (2001). Neuregulin-1-stimulated phosphorylation of GABP in skeletal muscle cells. Biochemistry 40, 5306–5312.CrossRefGoogle Scholar
Gugneja, S., Virbasius, J.V., & Scarpulla, R.C. (1995). Four structurally distinct, non-DNA-binding subunits of human nuclear respiratory factor 2 share a conserved transcriptional activation domain. Molecular and Cellular Biology 15, 102–111.CrossRefGoogle Scholar
Guo, A., Nie, F., & Wong-Riley, M. (2000). Human nuclear respiratory factor 2 alpha subunit cDNA: Isolation, subcloning, sequencing, and in situ hybridization of transcripts in normal and monocularly deprived macaque visual system. Journal of Comparative Neurology 417, 221–232.3.0.CO;2-4>CrossRefGoogle Scholar
Hendry, S.H. & Jones, E.G. (1988). Activity-dependent regulation of GABA expression in the visual cortex of adult monkeys. Neuron 1, 701–712.CrossRefGoogle Scholar
Hendry, S.H., Jones, E.G., & Burstein, N. (1988). Activity-dependent regulation of tachykinin-like immunoreactivity in neurons of monkey visual cortex. Journal of Neuroscience 8, 1225–1238.Google Scholar
Herdegen, T., Kovary, K., Buhl, A., Bravo, R., Zimmermann, M., & Gass, P. (1995). Basal expression of the inducible transcription factors c-Jun, JunB, JunD, c-Fos, FosB, and Krox-24 in the adult rat brain. Journal of Comparative Neurology 354, 39–56.CrossRefGoogle Scholar
Hevner, R.F. & Wong-Riley, M.T. (1991). Neuronal expression of nuclear and mitochondrial genes for cytochrome oxidase (CO) subunits analyzed by in situ hybridization: Comparison with CO activity and protein. Journal of Neuroscience 11, 1942–1958.Google Scholar
Hevner, R.F. & Wong-Riley, M.T. (1993). Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons. Journal of Neuroscience 13, 1805–1819.Google Scholar
Horton, J.C. (1984). Cytochrome oxidase patches: A new cytoarchitectonic feature of monkey visual cortex. Philosophical Transactions of the Royal Society B (London) 304, 199–253.CrossRefGoogle Scholar
Huntsman, M.M., Isackson, P.J., & Jones, E.G. (1994). Lamina-specific expression and activity-dependent regulation of seven GABAA receptor subunit mRNAs in monkey visual cortex. Journal of Neuroscience 14, 2236–2259.Google Scholar
Kadenbach, B., Jarausch, J., Hartmann, R., & Merle, P. (1983). Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure. Annals of Biochemistry 129, 517–521.CrossRefGoogle Scholar
Kaminska, B., Kaczmarek, L., & Chaudhuri, A. (1996). Visual stimulation regulates the expression of transcription factors and modulates the composition of AP-1 in visual cortex. Journal of Neuroscience 16, 3968–3978.Google Scholar
Kaur, R., Dikshit, K.L., & Raje, M. (2002). Optimization of immunogold labeling TEM: An ELISA-based method for evaluation of blocking agents for quantitative detection of antigen. Journal of Histochemistry and Cytochemistry 50, 863–873.CrossRefGoogle Scholar
LaMarco, K., Thompson, C.C., Byers, B.P., Walton, E.M., & McKnight, S.L. (1991). Identification of Ets- and notch-related subunits in GA binding protein. Science 253, 789–792.CrossRefGoogle Scholar
Lenka, N., Vijayasarathy, C., Mullick, J., & Avadhani, N.G. (1998). Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Progress in Nucleic Acid Research and Molecular Biology 61, 309–344.CrossRefGoogle Scholar
Livingstone, M.S. & Hubel, D.H. (1983). Specificity of cortico-cortical connections in monkey visual system. Nature 304, 531–534.CrossRefGoogle Scholar
Lund, J.S. (1973). Organization of neurons in the visual cortex, area 17, of the monkey (Macaca mulatta). Journal of Comparative Neurology 147, 455–496.CrossRefGoogle Scholar
Martin, M.E., Chinenov, Y., Yu, M., Schmidt, T.K., & Yang, X.Y. (1996). Redox regulation of GA-binding protein-alpha DNA binding activity. Journal of Biological Chemistry 271, 25617–25623.CrossRefGoogle Scholar
Nakatsu, S.L., Masek, M.A., Landrum, S., & Frenster, J.H. (1974). Activity of DNA templates during cell division and cell differentiation. Nature 248, 334–335.CrossRefGoogle Scholar
Nie, F. & Wong-Riley, M.T. (1995). Double labeling of GABA and cytochrome oxidase in the macaque visual cortex: Quantitative EM analysis. Journal of Comparative Neurology 356, 115–131.CrossRefGoogle Scholar
Nie, F. & Wong-Riley, M.T. (1996a). Differential glutamatergic innervation in cytochrome oxidase-rich and -poor regions of the macaque striate cortex: Quantitative EM analysis of neurons and neuropil. Journal of Comparative Neurology 369, 571–590.Google Scholar
Nie, F. & Wong-Riley, M.T. (1996b). Metabolic and neurochemical plasticity of gamma-aminobutyric acid-immunoreactive neurons in the adult macaque striate cortex following monocular impulse blockade: Quantitative electron microscopic analysis. Journal of Comparative Neurology 370, 350–366.Google Scholar
Nie, F. & Wong-Riley, M. (1999). Nuclear respiratory factor-2 subunit protein: correlation with cytochrome oxydase and regulation by functional activity in the monkey primary visual cortex. Journal of Comparative Neurology 404, 310–320.3.0.CO;2-4>CrossRefGoogle Scholar
Ning, G., Liang, H.L., Scheidt, M., Jacobs, P., Scarpulla, R., & Wong-Riley, M.T.T. (2002). Ultrastructural localization of a transcription factor for cytochrome oxidase, nuclear respiratory factor 2a and 2b subunits in visual cortical neurons. Society for Neuroscience Abstracts #658. 6.Google Scholar
Okuno, H., Kanou, S., Tokuyama, W., Li, Y.X., & Miyashita, Y. (1997). Layer-specific differential regulation of transcription factors Zif268 and Jun-D in visual cortex V1 and V2 of macaque monkeys. Neuroscience 81, 653–666.CrossRefGoogle Scholar
Ongwijitwat, S. & Wong-Riley, M.T.T. (2004). Functional analysis of the rat cytochrome c oxidase subunit 6A1 promoter in primary neurons. Gene 337, 163–171.Google Scholar
Parisi, M.A., Xu, B., & Clayton, D.A. (1993). A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro. Molecular Cellular Biology 13, 1951–1961.CrossRefGoogle Scholar
Peters, B., Kaiser, H.W., & Magin, T.M. (2001). Skin-specific expression of ank-3(93), a novel ankyrin-3 splice variant. Journal of Investigative Dermatology 116, 216–223.CrossRefGoogle Scholar
Scarpulla, R.C. (1997). Nuclear control of respiratory chain expression in mammalian cells. Bioenergy and Biomembranes 29, 109–119.CrossRefGoogle Scholar
Scarpulla, R.C. (2002). Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochimica et Biophysica Acta 1576, 1–14.Google Scholar
Seelan, R.S. & Grossman, L.I. (1997). Structural organization and promoter analysis of the bovine cytochrome c oxidase subunit VIIc gene. A functional role for YY1. Journal of Biological Chemistry 272, 10175–10181.Google Scholar
Seelan, R.S., Gopalakrishnan, L., Scarpulla, R.C., & Grossman, L.I. (1996). Cytochrome c oxidase subunit VIIa liver isoform. Characterization and identification of promoter elements in the bovine gene. Journal of Biological Chemistry 271, 2112–2120.Google Scholar
Shadel, G.S. & Clayton, D.A. (1993). Mitochondrial transcription initiation. Variation and conservation. Journal of Biological Chemistry 268, 16083–16086.Google Scholar
Sincich, L.C. & Horton, J.C. (2002). Divided by cytochrome oxidase: A map of the projections from V1 to V2 in macaques. Science 295, 1734–1737.CrossRefGoogle Scholar
Spector, D.L. (2003). The dynamics of chromosome organization and gene regulation. Annual Review of Biochemistry 72, 573–608.CrossRefGoogle Scholar
Virbasius, J.V. & Scarpulla, R.C. (1991). Transcriptional activation through ETS domain binding sites in the cytochrome c oxidase subunit IV gene. Molecular and Cell Biology 11, 5631–5638.CrossRefGoogle Scholar
Virbasius, J.V. & Scarpulla, R.C. (1994). Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: A potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proceedings of the National Academy of Sciences of the U.S.A. 91, 1309–1313.CrossRefGoogle Scholar
Virbasius, J.V., Virbasius, C.A., & Scarpulla, R.C. (1993). Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. Genes and Development 7, 380–392.CrossRefGoogle Scholar
Wong-Riley, M. (1979). Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Research 171, 11–28.CrossRefGoogle Scholar
Wong-Riley, M.T.T. (1988). Comparative study of the mammalian primary visual cortex with cytochrome oxidase histochemistry. In Vision: Structure and Function, ed. Yew, D.T., So, K.F. & Tsang, D.S.C., pp. 450–486. New Jersey: World Scientific Press.
Wong-Riley, M.T. (1989). Cytochrome oxidase: An endogenous metabolic marker for neuronal activity. Trends in Neuroscience 12, 94–101.CrossRefGoogle Scholar
Wong-Riley, M.T.T. (1994). Dynamic metabolic organization and plasticity revealed by cytochrome oxidase. In Cerebral Cortex. Vol. 10. Primate Visual Cortex, ed. Peters, A. & Rockland, K.S., pp. 141–200. New York: Plenum Press.
Wong-Riley, M. & Carroll, E.W. (1984). Effect of impulse blockage on cytochrome oxidase activity in monkey visual system. Nature 307, 262–264.CrossRefGoogle Scholar
Wong-Riley, M. & Riley, D.A. (1983). The effect of impulse blockage on cytochrome oxidase activity in the cat visual system. Brain Research 261, 185–193.CrossRefGoogle Scholar
Wong-Riley, M.T., Tripathi, S.C., Trusk, T.C., & Hoppe, D.A. (1989). Effect of retinal impulse blockage on cytochrome oxidase-rich zones in the macaque striate cortex: I. Quantitative electron-microscopic (EM) analysis of neurons. Visual Neuroscience 2, 483–497.Google Scholar
Wong-Riley, M., Anderson, B., Liebl, W., & Huang, Z. (1998). Neurochemical organization of the macaque striate cortex: Correlation of cytochrome oxidase with Na+K+ATPase, NADPH-diaphorase, nitric oxide synthase, and N-methyl-D-aspartate receptor subunit 1. Neuroscience 83, 1025–1045.CrossRefGoogle Scholar
Wong-Riley, M., Guo, A., Bachman, N.J., & Lomax, M.I. (2000). Human COX6A1 gene: Promoter analysis, cDNA isolation and expression in the monkey brain. Gene 247, 63–75.CrossRefGoogle Scholar
Worley, P.F., Christy, B.A., Nakabeppu, Y., Bhat, R.V., Cole, A.J., & Baraban, J.M. (1991). Constitutive expression of zif268 in neocortex is regulated by synaptic activity. Proceedings of the National Academy of Sciences of the U.S.A 88, 5106–5110.CrossRefGoogle Scholar
Yang, S.J., Liang, H.L., Ning, G., & Wong-Riley, M.T.T. (2004). Ultrastructural study of depolarization-induced translocation of NRF-2 transcription factor in cultured rat visual cortical neurons. European Journal of Neuroscience 19, 1153–1162.CrossRefGoogle Scholar
Yi, H., Leunissen, J., Shi, G., Gutekunst, C., & Hersch, S. (2001). A novel procedure for pre-embedding double immunogold-silver labeling at the ultrastructural level. Journal of Histochemistry and Cytochemstry 49, 279–284.CrossRefGoogle Scholar
Zhang, C. & Wong-Riley, M.T. (2000). Depolarizing stimulation upregulates GA-binding protein in neurons: A transcription factor involved in the bigenomic expression of cytochrome oxidase subunits. European Journal of Neuroscience 12, 1013–1023.CrossRefGoogle Scholar