Cell Membranes pp 219-246 | Cite as

Assembly and Establishment of Membrane-Cytoskeleton Domains During Differentiation

Spectrin as a Model System
  • W. James Nelson
  • Elias Lazarides


The multifunctional capability of the eukaryotic cell is expressed and regulated, to a great extent, by the cell type-specific biophysical properties of the plasma membrane. The plasma membrane is essentially a barrier comprising a phospholipid bilayer structure which acts also as a matrix onto which and into which a variety of specific proteins are attached. It is these proteins which selectively modify the structure and properties of the plasma membrane to create a wide variety of domains of distinctive morphology and function.


Terminal Differentiation Anion Transporter Stable Assembly Intestinal Brush Border Brain Spectrin 


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  1. Axelrod, D., Ravdin, P., Koppel, D. E., Schlesinger, J., Webb, W. W., Elson, E. L., and Podleski, T. R., 1976, Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers, Proc. Natl. Acad. Sci. USA 73: 4594–4598.PubMedCrossRefGoogle Scholar
  2. Bennett, V., 1982, The molecular basis for membrane—cytoskeleton association in human erythrocytes, J. Cell. Biochem. 18: 49–65.PubMedCrossRefGoogle Scholar
  3. Bennett, V., and Stenbuck, P., 1979a, Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin, J. Biol. Chem. 254: 2533–2541.PubMedGoogle Scholar
  4. Bennett, V., and Stenbuck, P. J., 1979b, The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes, Nature (London) 280: 468–473.CrossRefGoogle Scholar
  5. Bennett, V., and Stenbuck, P. J., 1980, Association between ankyrin and the cytoplasmic domain of band 3 isolated from the human erythrocyte membrane, J. Biol. Chem. 255: 2540–2548.PubMedGoogle Scholar
  6. Bennett, V., Davis, J., and Fowler, W. A., 1982, Brain spectrin, a membrane-associated protein related in structure and function to erythrocyte spectrin, Nature (London) 299: 126–131.CrossRefGoogle Scholar
  7. Ben—Ze’ev, A., Duerr, A., Solomon, F., and Penman, S., 1979, The outer boundary of the cyto-skeleton: a lamina derived from plasma membrane proteins, Cell 17: 859–865.CrossRefGoogle Scholar
  8. Blikstad, I., Nelson, W. J., Moon, R. T., and Lazarides, E., 1983, Synthesis and assembly of spectrin during avian erythropoiesis: Stoichiometric assembly but unequal synthesis of a-and 3-spectrin, Cell 32: 1081–1091.PubMedCrossRefGoogle Scholar
  9. Branton, D., Cohen, C. H., and Tyler, J., 1981, Interaction of cytoskeletal proteins on the human erythrocyte membrane, Cell 24: 24–32.PubMedCrossRefGoogle Scholar
  10. Brenner, S. L., and Korn, E. D., 1979, Spectrin-actin interaction. Phosphorylated and dephos-phorylated spectrin tetramers crosslink F-actin, J. Biol. Chem. 254: 8620–8627.PubMedGoogle Scholar
  11. Burns, N. R., Ohanian, V., and Gratzer, W. B., 1983, Properties of brain spectrin (fodrin), FEBS Lett. 153: 165–168.PubMedCrossRefGoogle Scholar
  12. Burridge, K., Kelly, T., and Mangeat, P., 1982, Nonerythrocyte spectrin: Actin—membrane attachment proteins occurring in many cell types, J. Cell Biol. 95: 478–486.PubMedCrossRefGoogle Scholar
  13. Dodge, J. T., Mitchell, C., and Hanahan, P. J., 1963, Preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes, Arch. Biochem. Biophys. 100: 119–130.PubMedCrossRefGoogle Scholar
  14. Gard, D. L., and Lazarides, E., 1980, The synthesis and distribution of desmin and vimentin during myogenesis in vitro, Cell 19: 263–275.PubMedCrossRefGoogle Scholar
  15. Glenney, J. R., Glenney, P., Osborn, M., and Weber, K., 1982a, An F-actin and calmodulinbinding protein from isolated intestinal brush borders has a morphology related to spectrin, Cell 28: 843–854.PubMedCrossRefGoogle Scholar
  16. Glenney, J. R., Glenney, P., and Weber, K., 1982b, F-actin-binding and crosslinking properties of porcine brain fodrin, a spectrin-related molecule, J. Biol. Chem. 257: 9781–9787.PubMedGoogle Scholar
  17. Glenney, J. R., Glenney, P., and Weber, K., 1982c, Erythroid spectrin, brain fodrin and intestinal brush border protein (TW260/240) are related molecules containing a common calmodulinbinding subunit bound to a variant cell type-specific subunit, Proc. Natl. Acad. Sci. USA 79: 4002–4005.PubMedCrossRefGoogle Scholar
  18. Gomer, R., and Lazarides, E., 1981, The synthesis and deployment of filamin in chicken skeletal muscle, Cell 23: 524–537.PubMedCrossRefGoogle Scholar
  19. Granger, B. L., and Lazarides, E., 1978, The existence of an insoluble Z disc scaffold in chicken skeletal muscle, Cell 15: 1253–1268.PubMedCrossRefGoogle Scholar
  20. Granger, B. L., and Lazarides, E., 1979, Desmin and vimentin coexist at the periphery of the myofibril Z disc, Cell 18: 1053–1063.PubMedCrossRefGoogle Scholar
  21. Granger, B. L. and Lazarides, E., 1980, Synemin: a new high molecular weight protein associated with desmin and vimentin filaments in muscle, Cell 22: 727–738.PubMedCrossRefGoogle Scholar
  22. Granger, B. L., Repasky, E. A., and Lazarides, E., 1983, Synemin and vimentin are components of intermediate filaments in avian erythrocytes, J. Cell Biol. 92: 299–312.CrossRefGoogle Scholar
  23. Huestis, W. H., Nelson, M. J., and Ferrell, J. E., Jr., 1981, Calmodulin-dependent spectrin kinase activity in human erythrocytes, in: Erythrocyte Membranes: Recent Clinical and Experimental Advances (W. C. Kruckeberg, J. W. Eaton, and G. J. Brewer, eds.), Liss, New York, pp. 137–152.Google Scholar
  24. Jacobson, M., 1978, Comments on assembly of complex neuronal systems, in: Developmental Neurobiology, 2nd ed., Plenum Press, New York, pp. 75–92.Google Scholar
  25. Kakiuchi, S., Sobue, K., Kanda, K., Morimoto, K., Tsukati, S., Tsukita, S., Ishikawa, H., and Kurokawa, M., 1982, Correlative biochemical and morphological studies of brain calspectin: A spectrin-like calmodulin-binding protein, Biomed. Res. 3: 400–410.Google Scholar
  26. Koch, G. L. E., and Smith, M. J., 1978, An association between actin and the major histocompatibility antigen H-2, Nature (London) 273: 274–278.CrossRefGoogle Scholar
  27. Lazarides, E., 1980, Intermediate filaments as mechanical integrators of cellular space, Nature 283: 249–256.PubMedCrossRefGoogle Scholar
  28. Lazarides, E., and Granger, B. L., 1983, Transcytoplasmic integration in avian erythrocytes and striated muscle, Modern Cell Biol. 2: 143–162.Google Scholar
  29. Lazarides, E., and Nelson, W. J., 1982, Expression of spectrin in nonerythroid cells, Cell 31:505–508. Lazarides, E., and Nelson, W. J., 1983a, Erythrocyte and brain forms of spectrin in cerebellum: distinct membrane-cytoskeletal domains in neurons, Science 220: 1295–1296.CrossRefGoogle Scholar
  30. Lazarides, E., and Nelson, W. J., 1983b, Erythrocyte form of spectrin in cerebellum: appearance at a specific stage in the terminal differentiation of neurons, Science 222: 931–933.PubMedCrossRefGoogle Scholar
  31. Lehto, V.—P., and Virtanen, I., 1983, Immunolocalization of a novel, cytoskeleton-associated poly-peptide of Mr 230,000 daltons (p230), J. Cell Biol. 96: 703–716.PubMedCrossRefGoogle Scholar
  32. Levine, J., and Willard, M., 1981, Fodrin: axonally transported polypeptides associated with the internal periphery of many cells, J. Cell Biol. 90: 631–643.PubMedCrossRefGoogle Scholar
  33. Levine, J., and Willard, M., 1983, Redistribution of fodrin (a component of the cortical cytoplasm) accompanying capping of cell surface molecules, Proc. Natl. Acad. Sci. USA 80: 191–195PubMedCrossRefGoogle Scholar
  34. Lux, S. E., John, K. M., and Karnovsky, M. J., 1976, Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells, J. Clin. Invest. 58: 955–963.CrossRefGoogle Scholar
  35. Mescher, M. F., Jose, M. J. L., and Balk, S. P., 1981, Actin-containing matrix associated with the plasma membrane of murine tumor and lymphoid cells, Nature (London) 289: 139–144.CrossRefGoogle Scholar
  36. Moon, R. T., and Lazarides, E., 1983,13-spectrin limits the assembly of a-spectrin onto membranes following synthesis in a chicken erythroid cell lysate. Nature (London) 305: 62–65.Google Scholar
  37. Mugnaini, E., 1969, Ultrastructural studies on the cerebellar histogenesis. II. Maturation of nerve cell populations and establishment of synaptic connections in the cerebellar cortex of the chick, in: Proceedings of the First International Symposium of the Institute for Biomedical Research: Neurobiology of Cerebellar Evolution and Development ( R. Llinas, ed.), Institute for Biomedical Research, Chicago, Illinois, 1969, p. 749–782.Google Scholar
  38. Nelson, G. A., Andrews, M. L., and Karnovsky, M. J., 1983, Control of erythrocyte shape by calmodulin, J. Cell Biol. 96: 730–735.PubMedCrossRefGoogle Scholar
  39. Nelson, W. J., and Lazarides, E., 1983a, Expression of the 0-subunit of spectrin in nonerythroid cells, Proc. Natl. Acad. Sci. USA 80: 363–367.PubMedCrossRefGoogle Scholar
  40. Nelson, W. J., and Lazarides, E., 1983b, Switching of the subunit composition of muscle spectrin during myogenesis in vitro, Nature (London) 304: 364–368.CrossRefGoogle Scholar
  41. Nelson, W. J., Granger, B. L., and Lazarides, E., 1983a, Avian lens spectrin: subunit composition compared with erythrocyte and brain spectrin, J. Cell Biol. 91: 1271–1276.CrossRefGoogle Scholar
  42. Nelson, W. J., Colaco, C. A. L. S., and Lazarides, E., 1983b, Involvement of spectrin in cell-surface receptor capping in lymphocytes, Proc. Natl. Acad. Sci. USA 80: 1626–1630.PubMedCrossRefGoogle Scholar
  43. Nicolson, G. Z., 1976, Transmembrane control of the receptors on normal and tumor cells. I. Cytoplasmic influence over cell surface components, Biochim. Biophys. Acta 457: 57–108.PubMedCrossRefGoogle Scholar
  44. Palek, J., Liu, S. C., and Liu, P. A., 1978, Crosslinking of the nearest membrane neighbors in ATP-depleted, calcium-enriched and irreversibly sickled red cells, in: Erythrocyte Membranes: Recent Clinical and Experimental Advances (W. C. Kruckeberg, J. W. Eaton, and G. J. Brewer, eds.), Liss, New York, pp. 75–88.Google Scholar
  45. Palfrey, M. C., Schieber, W., and Greengard, P., 1982, A major calmodulin-binding protein common to various vertebrate tissues, Proc. Natl. Acad. Sci. USA 79: 3780–3784.PubMedCrossRefGoogle Scholar
  46. Pierbon—Bormioli, S., 1981, Transverse sarcomere filamentous systems: “Z- and M-lines,” J. Musc. Res. Cell Motil. 2: 401–408.CrossRefGoogle Scholar
  47. Pollard, T. M., and Weihing, R. R., 1974, Actin and myosin and cell movement, CRC Crit. Rev. Biochem. 2: 1–65.PubMedCrossRefGoogle Scholar
  48. Repasky, E. A., Granger, B. L., and Lazarides, E., 1982, Widespread occurrence of avian spectrin in nonerythroid cells, Cell 29: 821–833.PubMedCrossRefGoogle Scholar
  49. Schliwa, M., 1981, Proteins associated with cytoplasmic actin, Cell 25: 587–590.PubMedCrossRefGoogle Scholar
  50. Shekman, R., and Singer, S. J., 1976, Clustering and endocytosis of membrane receptors can be induced in mature erythrocytes of neonatal but not adult humans, Proc. Natl. Acad. Sci. USA 73: 4075–4079.CrossRefGoogle Scholar
  51. Shimono, T., Nosaka, S., and Sasaki, K., 1976, Electrophysiological study on the postnatal de- velopment of neuronal mechanisms in the rat cerebellar cortex, Brain Res. 108: 279–294.PubMedCrossRefGoogle Scholar
  52. Shimo—Oka, T., and Watanabe, Y., 1981, Stimulatin of actomyosin Mg’-ATPase activity by a brain microtubule-associated protein fraction. High-molecular-weight actin-binding protein is the stimulating factor, J. Biochem. 90: 1297–1307.Google Scholar
  53. Sieting, G. E., Jr., and Lorand, L., 1978, Ca++ -modulated crosslinking of membrane proteins in intact erythrocytes, in: Erythrocyte Membranes: Recent Clinical and Experimental Advances (W. C. Kruckeberg, J. W. Eaton, and G. J. Brewer, eds.), Liss, New York, pp. 25–32.Google Scholar
  54. Singer, S. J., and Nicolson, G. L., 1972, The fluid mosaic model of the structure of cell membranes. Science (Washington, D. C.) 175: 720–731.Google Scholar
  55. Street, S. F., 1983, Lateral transmission of tension in frog myofibers: A myofibrillar network and transverse cytoskeletal connections are possible transmitters, J. Cell. Physiol. 114: 346–364.PubMedCrossRefGoogle Scholar
  56. Sobue, K., Kauda, K., and Kakiuchi, S., 1982, Solubilization and partial purification of proteinGoogle Scholar
  57. kinase systems from brain membranes that phosphorylate calspectin, FEBS Lett 150:185–190.Google Scholar
  58. Tiegs, O. W., 1954, The flight muscles of insects—their anatomy and histology; with some observations on the structure of striated muscle in general, Roy. Soc. Lond. Phil. Trans. Ser. B 238: 221–348.CrossRefGoogle Scholar
  59. Tokuyasu, K. T., Shekman, R., and Singer, S. J., 1979, Domains of receptor mobility and endocytosis in the membranes of neonatal human erythrocytes and reticulocytes are deficient in spectrin, J. Cell Biol. 80: 481–486.PubMedCrossRefGoogle Scholar
  60. Tyler, J., Margreaves, W., and Branton, D., 1979, Purification of two spectrin binding proteins: biochemical and electron microscopic evidence for site-specific reassociation between spectrin and bands 2.1 and 4.1 to spectrin, J. Biol. Chem. 255: 7034–7039.Google Scholar
  61. Warwick, R., and Williams, P. L. (eds.), 1973, Gray’s Anatomy. Saunders, London, p. 871. Weihing, R. R., 1979, The cytoskeleton and plasma membrane, in: Methods and Achievements in Experimental Pathology; Cel Biology, Volume 8 (G. Gabbiani, ed.), Karger, Basel, pp. 42–109.Google Scholar
  62. Yu, J., Fischman, D. A., and Steck, T. L., 1973, Selective solubilization of proteins and phos-pholipids from red blood cell membrane by nonionic detergents, J. Supramol. Struct. 1: 233–248.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • W. James Nelson
    • 1
  • Elias Lazarides
    • 1
  1. 1.Division of BiologyCalifornia Institute of TechnologyPasadenaUSA

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