Plasticity in Astrocytic Phenotypes

A Role For Protein Kinase C, Tyrosine Kinases, and Cytoskeleton Signaling
  • Dimitra A. Mangoura
  • C. Pelletiere
  • D. Wang
  • N. Sakellaridis
  • V. Sogos
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 429)


Neurons and astrocytes derive from common progenitor ectodermal cells. The neuronal progenitors actively proliferate early in development, as the development of the neural tube and the CNS vesicles progresses. Neuroblast proliferation ceases quite early, and in most species it precedes the burst of astroblastic proliferation. During the massive proliferation of neurons, astrocytes exist in small numbers and with one identifiable phenotype, namely radial glia (Cameron and Rakic, 1994). After their final mitotic division in the subventricular zone, neurons migrate, populate specific laminae in the developing brain, elaborate processes, and form functional synapses. While neurons are migrating for more precise formation of CNS layers, astroblasts proliferate, so that in the adult brain the ratio is 9 astrocytes to 1 neuron. During the course of differentiation from a glioblast to a mature astrocyte, astrocytes undergo dynamic shape-function changes. Most intermediate and differentiated phenotypes of astrocytes are characterized by expression of specific cytoskeletal proteins and the acquisition of specific shape (reviewed in Cameron and Rakic, 1991). After final positioning and cell programmed death of neurons and astrocytes, the patterning of the brain remains a very dynamic process. It now includes constant remodeling of synapses, and continuous differentiation and proliferation of astrocytes, or differentiation of neurons and oligodendrocytes.


Chick Embryo Phorbol Ester Glutamine Synthetase Activity Cytoskeleton Protein Astrocytic Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baltuch, G. H., N. P. Dooley, K. M. Rostworowski, J. G. Villemure, and V. W. Yong. 1995. Protein kinase C isoforms alpha overexpression in C6 glioma cells and its role in cell proliferation. J. Neuro Oncol. 24: 241–250.CrossRefGoogle Scholar
  2. Barry, S. T., and C. D.R. 1994. The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated with increased tyrosine phosphorylation and the recruitment of both pp125FAK and protein kinase C-6 to focal adhesions. J. Cell Sci. 107: 2033–2045.PubMedGoogle Scholar
  3. Bender, A. S. J. T. Neary, J. Blicharska, L. O. Norenberg, and M. D. Norenberg. 1991. Role of calmodulin and protein kinase C in astrocytic volume regulation. J. Neurochem. 58: 1874–1882.CrossRefGoogle Scholar
  4. Bignami, A., and D. Dahl. 1976. Immunofluorescence studies with antibodies to astrocyte-specific protein (GFA) in mammalian and submammalian vertebrates. Neuropathol Appl. Neurobiol. 2: 99–111.CrossRefGoogle Scholar
  5. Billah, M. M., S. Eckel, T. J. Mullmann, R. W. Egan, and M. I. Siegel. 1989. Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophile. Involvement of phosphatidate phosphohydrolase in signal transduction. J. Biol. Chem. 264: 17069–77.PubMedGoogle Scholar
  6. Billah, M. M., J. K. Pai, T. J. Mullmann, R. W. Egan, and M. I. Siegel. 1989. Regulation of phospholipase D in HL-60 granulocytes. Activation by phorbol esters, diglyceride, and calcium ionophore via protein kinase-independent mechanisms. J. Biol. Chem. 264: 9069–76.PubMedGoogle Scholar
  7. Cameron, R. S., and P. Rakic. 1991. Glial cell lineage in the cerebral cortex: a review and synthesis. Glia. 4: 124–137.PubMedCrossRefGoogle Scholar
  8. Cameron, R. S., and P. Rakic. 1994. Identification of membrane proteins that comprise the plasmalemmal junction between migrating neurons and radial glial cells. J Neuroscience. 14: 3139–3155.Google Scholar
  9. Chavez, R. A., r. S. Mille, and H. Moore. 1996. A biosynthetic regulated secretory pathway in constitutive secretory cells. J. Cell Biol. 1: 177–91.Google Scholar
  10. Cook, S. J., and M. J. O. Wakelam. 1992. Epidermal growth factor increases sn-1,2-diacylglycerol levels and activates phospholipase D-catalysed phosphatidylcholine breakdown in Swiss 3T3 cells in the absence of inositol-lipid hydrolysis. Biochem. J. 285: 247–253.PubMedGoogle Scholar
  11. Exton, J. H. 1990. Signalling through phosphatidylcholine breakdown. J. Biol. Chem. 265: 1–4.PubMedGoogle Scholar
  12. Fanti, W., A. Muslin, A. Kikuchi, J. Martin, A. MacNicol, R. Gross, and L. Williams. 1994. Activation of Raf–I by I4–3–3 proteins. Nature. 371: 612–6I4.Google Scholar
  13. Gustaysson, L., and E. Hansson. 1990. Stimulation of phospholipase D activity by phorbol esters in cultured astrocytes. J. Nearochem. 42: 737–42.CrossRefGoogle Scholar
  14. Harrison, B. C., and P. L. Mobley. 1992. Phosphorylation of glial fibrillary acidic protein and vimentin by cytoskeletal-associated intermediate filament protein kinase activity in astrocytes. J. Neurochem. 58: 320–327.PubMedCrossRefGoogle Scholar
  15. Rundle, B., T. McMahon, J. Dadgar, and R. Messing. 1995. Overexpression of PKC-a enhances nerve growth factor-induced phosphorylation of mitogen-activated protein kinases and neurite outgrowth. 1. Biol. Chem. 260: 30134–30140.Google Scholar
  16. Isaaks, W. B., R. K. Cook, J. C. Van Atta, C. M. Redmond, and A. B. Fulton, J. Biol. Chem., 264 17953–17960.Google Scholar
  17. 1989.
    Assembly of vimentin in culture varies with cell types. J. Biol. Chem. 264: 17953–17960.Google Scholar
  18. Janz, R., and T. Sudhof. 1995. A systematic approach to studying synaptic function in vertebrates. Cold Spring Harbor Symposia on Quantitative Biology. 60: 309–14.PubMedCrossRefGoogle Scholar
  19. Jiang, H., J. Luo, T. Urano, P. Frankel, Z. Lu, D. Foster, and L. Feig. 1995. Involvement of Ral GTPase in v-Srcinduced phospholipase D activation. Nature. 378: 409–12.PubMedCrossRefGoogle Scholar
  20. Kentroti, S., and A. Vernadakis. 1997. Differential expression in glial cells derived from chick embryo cerebral hemispheres at an advance stage of development. J. Neurosci. Res. 47: 322–331.PubMedCrossRefGoogle Scholar
  21. Kozma, R., S. Ahmed, A. Best, and L. Lim. 1995. The Ras-related Cdc42Hs and Bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol. Cell. Biol. 15: 1942–1952.PubMedGoogle Scholar
  22. Liscovitch, M., and C.-C. V. 1996. Enzymology of mammalian phospholipases D: in vitro studies. Chenmisty and Physics of Lipids 80. 80: 37–44.CrossRefGoogle Scholar
  23. Luo, L., Hensch, T.K.,, L. Ackerman, S. Barbels, L. Y. Jan, and Y. N. Jan. 1996. Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. Nature. 379: 837–840.Google Scholar
  24. Mangoura, D. 1994. PKC-dependent regulation of glia phenotypes: effects on vimentin assembly. Hitl. Devi. Neurosci. 12: 1–80.CrossRefGoogle Scholar
  25. Mangoura, D. 1995. Brain Res. In press.Google Scholar
  26. Mangoura, D., and G. Dawson. 1997. Programmed cell death in cortical astrocytes from chick embryo cerebral hemisphere cultures is associated with activation of protein kinase pk60 and ceramide formation. J. Neurochem.Google Scholar
  27. Mangoura, D., C. Pelletiere, and G. Dawson. 1993. Astrocytic phenotype regulation by PLD and kinases in chick embryo culture. Soc. Neurosci Abstract. 28: 3: 43.Google Scholar
  28. Mangoura, D., N. Sakellaridis, J. Jones, and A. Vernadakis. 1989. Early and late passage C-6 glial cell growth: similarities with primary glial cell in culture. J. Neurosci. 14: 941–947.Google Scholar
  29. Mangoura, D., N. Sakellaridis, and A. Vernadakis. 1986. Factors influencing neuronal growth in primary cultures derived from 3- day-old chick embryos. Int. J. Devi. Neurosci. 6: 89–102.CrossRefGoogle Scholar
  30. Mangoura, D., N. Sakellaridis, and A. Vernadakis. 1988. Cholinergic neurons in cultures derived from three, six or eight-day-old chick embryos: a biochemical and immunocytochemical study. Brain Res. 40: 25–46.CrossRefGoogle Scholar
  31. Mangoura, D., N. Sakellaridis, and A. Vernadakis. 1990. Evidence for plasticity in phenotypic neurotransmitter expression in culture. Del,. Brain Res. 51: 93–101.Google Scholar
  32. Mangoura, D., V. Sogos, and G. Dawson. 1993. PKC-c is a developmentally regulated, neuronal isoform inthe chick embryo CNS chick embryo. J. Neurosci. Res. 35: 488–498.PubMedCrossRefGoogle Scholar
  33. Mangoura, D., V. Sogos, and G. Dawson. 1995. Phorbol ester and PKC signalling regulate proliferation, vimentin cytoskeleton assembly and glutamine synthetase activity of chick embryo cerebrum astrocytes in culture. Brain Res. 87: 1–11.CrossRefGoogle Scholar
  34. Mangoura, D., V. Sogos, C. Pelletiere, and G. Dawson. 1995. Differential regulation of phospholipases C and D by phorbol esters and the physiological activators carbachol and glutamate in astrocytes from chick embryo cerebrum and cerebellum. Brain Res. 87: 12–21.CrossRefGoogle Scholar
  35. Mangoura, D., and A. Vernadakis. 1988. Gabaergic neurons in cultures derived from three, six or eight-day-old chick embryos: a biochemical and immunocytochemical study. Dee Brain Res. 40: 37–46.CrossRefGoogle Scholar
  36. Martinez-Hernandez, A., K. P. Bell, and M. D. Norenberg. 1977. Glutamine-synthetase-glial localization in the brain. Science. 195: 1356–1358.PubMedCrossRefGoogle Scholar
  37. Mobley, P. L., S. L. Scott. and E. G. Cruz. 1986. Protein kinase C in astrocytes: a determinant of cell morphology. Brain Res. 398: 366–369.Google Scholar
  38. Morrison-Bogorad, M., S. Pardue, D. McIntire, and E. Miller. 1994. Cell size and the heat-shock response in rat brain. Journal of Neurochemistry. 63: 857–867.PubMedCrossRefGoogle Scholar
  39. Neary, J. T. L.-O. -. B. Norenberg, and M. D. Norenberg. 1986. Calcium-activated, phospholipid-dependent protein kinase and protein substrates in primary cultures of astrocytes. Brain Res. 385: 420–424.PubMedCrossRefGoogle Scholar
  40. Nedergaard, M. 1994. Direct signalling from astrocytes to neurons in cultures of mammalian brain cell. Science. 263: 1768–1771.PubMedCrossRefGoogle Scholar
  41. Nishizuka, Y. 1995. Protein kinase C and lipid signaling for sustained cellular responses. FASFB Journal. 9: 484–96.Google Scholar
  42. Oppenheim, R. 1991. Cell death during development of the nervous system. Annual Reviews of Neuroscience. 14: 453–501.CrossRefGoogle Scholar
  43. Parker, K. K., M. D. Norenberg, and A. Vernadakis. 1980. `Transdifferentiation“ of C-6 glial cells in culture. Science. 208: 179–181.Google Scholar
  44. Peletiere, Wang, and Mangiura. 1997.Google Scholar
  45. Pelletiere, C., S. Leung, N. Sakellaridis, and D. Mangoura. 1995. Coupling of the prolactin receptor to tyrosine kinases regulate s activation of PLD, STAT9I and mitosis. Soc. Neuroscience,. 21: 562.Google Scholar
  46. Rasouly, D., E. Rahamim, I. Ringel, I. Ginzburg, C. Muarakata, Y. Matsuda, and P. Lazarovici. 1994. Neurites induced by staurosporinc in PC’12 cells are resistant to colchicine and express high levels of tau proteins. Molecular Pharmacology. 45: 29–35.PubMedGoogle Scholar
  47. Ron, D., C. Chen, J. Caldwell, L. Jamieson, E. Orr, and D. Mochly-Rosen. 1994. Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. Proceeli.Natì.Acal.Sci. USA. 91: 839–843.CrossRefGoogle Scholar
  48. Sakellaridis, N., D. Bau. D. Mangoura, and A. Vernadakis. 1983. Developmental profiles of glial enzyme sin the chick embryo: in vivo and in culture. Neurochem. Intern. 5: 685–689.CrossRefGoogle Scholar
  49. Sakellaridis, N., Mangoura D, and V. A. 1984. Glial cell growth in culture: influence of living cell substrata. Neurochem. Res. 9: 1469–1483.CrossRefGoogle Scholar
  50. Sakellaridis, N., D. Mangoura, and A. Vernadakis. 1986. Effects of neuron conditioned medium and fetal calf serum content on glial growth in dissociated cultures. Develop. Brain Res. 27: 31–41.CrossRefGoogle Scholar
  51. Sakellaridis, N., D. Mangoura, and A. Vernadakis, 1986. Effects of opiates on the growth of neuron-enriched cultures from chick embryonic brain. J. Develop. Neurosci. 4: 293–303.CrossRefGoogle Scholar
  52. Tsai HM, Garber BB. and L. LMH. 1981.3H-thymidine autoradiographic analysis of telencephalic histogenesis in the embryo. I Neuronal birthdays of telencephalic compartments in situ. J. Comp. Neurol. 198: 275–292.Google Scholar
  53. Vernadakis, A., and D. Mangoura. 1988. Factors influencing glial growth in culture: Nutrients and cell-secreted factors. In Nutrition, Growth and Cancer. G. P. Tryfiates and K. N. Prasad, editors. Alan R. Liss, Inc., New York. 57–79.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Dimitra A. Mangoura
    • 1
  • C. Pelletiere
    • 1
  • D. Wang
    • 1
  • N. Sakellaridis
    • 1
  • V. Sogos
    • 1
  1. 1.Department of Pediatrics and Committee on NeurobiologyThe University of ChicagoChicagoUSA

Personalised recommendations