Advertisement

The Role of Intermediate (10-nm) Filaments in the Development and Integration of the Myofibrillar Contractile Apparatus in the Embryonic Mammalian Heart

  • John W. Fuseler
  • Jerry W. Shay
  • Howard Feit

Abstract

Most eukaryotic cells possess three major distinct classes of fibrous organelles that are independently organized and function as elements of the cytoskeleton. These elements of the cytoskeleton include microtubules (25 nm), which form elaborate cytoplasmic networks; actin or thin filaments (6 nm), which form cytoplasmic stress fibers; and the intermediate filaments (10 nm). The term “intermediate” filaments has been applied to this third class of cytoplasmic fibrous proteins because their mean diameter at the ultrastructural level lies between the mean diameter of actin and microtubules. Investigations have shown that both actin (Clarke and Spudeck, 1977; Pollard and Werhing, 1974; Stossel, 1978) and microtubules (Stephens and Edds, 1976) are involved in various aspects of cell motility and also in the movement of cellular organelles. The role of the intermediate filaments in cell function is unresolved at present. The intermediate filaments were initially regarded as a disaggregation, or degradation product, or myosin and/or microtubules and thus until recently attracted little attention. Current biochemical and immunofluorescent methods have established the intermediate filaments as a distinct class of cytoplasmic proteins that differ with respect to the physical properties of their subunits. In contrast to the proteins actin and tubulin, which are the major structural protein subunits of microfilaments and microtubules, respectively, the intermediate-filament proteins do not appear to be highly conserved (Bennett et al., 1979; Lazarides and Balzer, 1978; Shelanski and Liem, 1979) and exhibit a relatively high degree of tissue specificity. The intermediate filaments have been divided into several subclasses on the basis of biochemical and immunochemical data, and their constituent proteins have been named accordingly. These subclasses at present include: (1) prekeratin tonofilaments found in epithelial cells (Franke et al.,1978a,b, 1979b; Sun et al., 1979) and cells of epithelial origin; (2) vimentin or decamin filaments (Bennett et al., 1978b, 1979; Franke et al.,1978a, 1979a) found in fibroblasts and other cells of mesenchymal orgin; (3) desmin filaments (Izant and Lazarides, 1974; Lazarides and Hubbard, 1976; Lazarides, 1978a; Lazarides and Balzer, 1978) or skeletin (Campbell et al.,1979) of smooth muscle, which have also been identified in the cytoplasm and Z lines of skeletal and cardiac muscle; (4) neurofilaments of neurons; and (5) glial filaments, which are present in astrocytes (Shelanski and Liem, 1979) but not in all types of glial cells (Liem et al., 1978; Schlaepfer, 1977; Schlaepfer and Lynch, 1977). Current studies have shown that it is not uncommon to find two of these classes of intermediate filaments coexisting in the same cell type. It is also quite possible that more than two classes of intermediate filaments can be present in a single cell type (Lazarides, 1980).

Keywords

Intermediate Filament Thin Filament Cell Margin Actin Stress Fiber Intercalate Disk 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allen, E. R., and Pepe, F. A., 1965, Ultrastructure of developing muscle cells in the chick embryo, Am. J. Anat. 116: 115.CrossRefGoogle Scholar
  2. Behrendt, H., 1977, Effect of anabolic steroids on rat heart muscle cells. I. Intermediate filaments, Cell Tissue Res. 180: 303.CrossRefGoogle Scholar
  3. Bennett, G. S., Fellini, S. A., and Holtzer, H., 1978a, Immunofluorescent visualization of 100, filaments in different cultured chick embryo cell types, Differentiation 12: 71.CrossRefGoogle Scholar
  4. Bennett, G. S., Fellini, S. A., Croop, J. M., Otto, J. J., Bryant, J., and Holtzer, H., 1978b, Differences among 100A-filament subunits from different cell types, Proc. Natl. Acad. Sci. U.S.A. 75: 4364.CrossRefGoogle Scholar
  5. Bennett, G. S., Fellini, S. A., Toyama, Y., and Holtzer, H., 1979, Redistribution of intermediate filament subunits during skeletal myogenesis and maturation in vitro, J. Cell Biol. 82: 577.CrossRefGoogle Scholar
  6. Bignami, A., Eng, L. F., Dahl, D., and Uyeda, C. T., 1972, Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence, Brain Res. 43: 429.CrossRefGoogle Scholar
  7. Blose, S. H., and Chacho, S. J., 1976, Rings of intermediate (100A) filament bundles in the perinuclear region of vascular endothelial cells: Their mobilization by colcemid and mitosis, J. Cell Biol. 70: 459.CrossRefGoogle Scholar
  8. Blose, S. H., Shelanski, M. L., and Chacho, S., 1977, Localization of bovine brain filament antibody on intermediate (100A) filaments in guinea pig vascular endothelial cells and chick cardiac muscle cells, Proc. Natl. Acad. Sci. U.S.A. 74: 662.CrossRefGoogle Scholar
  9. Bollon, A. P., Nath, K., and Shay, J. W., 1977, Establishment of contracting heart muscle cell cultures, Tissue Culture Assoc. Man. 3: 637.Google Scholar
  10. Campbell, G. R., Campbell, J. C., Stewart, U. G., Small, J. V., and Anderson, P., 1979, Antibody staining of 10 nm (100-A) filaments in cultured cardiac and skeletal muscle cells, J. Cell Sci. 37: 303.Google Scholar
  11. Caron, J. M., and Berlin, R. D., 1979, Interaction of microtubule proteins with phospholipid vesicles, J. Cell Biol. 81: 665.CrossRefGoogle Scholar
  12. Clarke, M., and Spudeck, J. A., 1977, Nonmuscle contractile proteins: The role of actin and myosin in cell motility and shape determination, Annu. Rev. Biochem. 46: 797.CrossRefGoogle Scholar
  13. Cooke, P. H., 1976, A filamentous cytoskeleton in vertebrate smooth muscle fibers, J. Cell Biol. 68: 539.CrossRefGoogle Scholar
  14. Cooke, P. H., and Chase, R. H., 1971, Potassium chloride-insoluble myofilaments in vertebrate smooth muscle cells, Exp. Cell Res. 66: 417.CrossRefGoogle Scholar
  15. Davison, P. F., and Winslow, B., 1974, The protein subunit of calf brain neurofilament, Neurobiology 5: 119.CrossRefGoogle Scholar
  16. Eckert, B. S., Koons, S. J., Schantz, A. W., and Zobel, C. R., 1980, Association of creatine phosphokinase with the cytoskeleton of cultured mammalian cells, J. Cell Biol. 86: 1.CrossRefGoogle Scholar
  17. Eng, L. F., Vanderhaeghen, J. J., Bignami, A., and Gerstl, B., 1971, An acidic protein isolated from fibrous astrocytes, Brain Res. 28: 351.CrossRefGoogle Scholar
  18. Eriksson, A., and Thornell, L.-E., 1979, Intermediate (skeletin) filaments in heart Purkinje fibers: A correlative morphological and biochemical identification with evidence of a cytoskeletal function, J. Cell Biol. 80: 231.CrossRefGoogle Scholar
  19. Eriksson, A., Thornell, L.-E., and Stigbrand, T., 1977, Cytoskeletal filaments of heart conducting system localized by antibody against 55,000 dalton protein, Experientia 34: 792.CrossRefGoogle Scholar
  20. Feit, H., Neudeck, U., and Shay, J. W., 1977, Anomalous electrophoretic properties of brain filament protein subunits, Brain Res. 133: 341.CrossRefGoogle Scholar
  21. Ferrans, V. J., and Roberts, W. C., 1973, Intermyofibrillar and nuclear myofibrillar connections in human and canine myocardium: An ultrastructure study, J, Mol. Cell. Cardiol. 5: 247.CrossRefGoogle Scholar
  22. Franke, W. W., Schmid, E., Osborn, M., and Weber, K., 1978a, Different intermediate-sized filaments distinguished by immunofluorescence microscopy, Proc. Natl. Acad. Sci. U.S.A. 75: 5034.CrossRefGoogle Scholar
  23. Franke, W. W., Weber, K., Osborn, M., Schmid, E., and Freudenstein, C., 1978b, Antibody to prekeratin: Decoration of tonofilament-like arrays in various cells of epithelial character, Exp. Cell Res. 116: 429.CrossRefGoogle Scholar
  24. Franke, W. W., Schmid, E., Osborn, M., and Weber, K., 1979a, Intermediate-sized filaments of human endothelial cells, J. Cell Biol. 81: 570.CrossRefGoogle Scholar
  25. Franke, W. W., Schmid, E., Weber, K., and Osborn, M., 1979, Hela cells contain intermediate-sized filaments of the prekeratin type, Exp. Cell Res. 118: 95.CrossRefGoogle Scholar
  26. Fuseler, J. W., 1975, Temperature dependence of anaphase chromosome velocity and microtubule depolymerization rate, J. Cell Biol. 89: 737.Google Scholar
  27. Garamvölgyi, N., 1965, Inter-Z-bridges in the flight muscle of the bee, J. Ultrastruct. Res. 13: 435.CrossRefGoogle Scholar
  28. Gard, D. L., Bell, P. B., and Lazarides, E., 1979, Coexistence of desmin and the fibroblastic intermediate filament subunit in muscle and non-muscle cells: Identification and comparative peptide analysis, Proc. Natl. Acad. Sci. U.S.A. 76: 3894.CrossRefGoogle Scholar
  29. Goldman, R. D., and Knipe, D. M., 1973, Functions of cytoplasmic fibers in non-muscle cell motility, in: The Mechanism of Muscle Contraction, Cold Spring Harbor Symp. Quant. Biol. 37: 523. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  30. Granger, B. L., and Lazarides, E., 1978, The existence of an insoluble Z disc scaffold in chicken skeletal muscle, Cell 15: 1253.CrossRefGoogle Scholar
  31. Granger, B. L., and Lazarides, E., 1979, Desmin and vimentin coexist at the periphery of myofibril Z disc, Cell 18: 1053.CrossRefGoogle Scholar
  32. Granger, B. L., Gard, D. L., and Lazarides, E., 1979, The coexistence of desmin and vimentin in developing and mature chicken skeletal muscle and their association with myofibril disks, J. Cell Biol. 83: 314a.Google Scholar
  33. Gudrun, B. S., Fellini, S. A., Toyama, Y, and Holtzer, H., 1979, Redistribution of intermediate filament subunits during skeletal myogenesis and maturation in vitro, J. Cell Biol. 82: 577.CrossRefGoogle Scholar
  34. Holtrap, M. E., Raisz, L. G., and Simmons, H. A., 1974, The effects of parathyroid hormone, colchicine, and calcitonin on the ultrastructure and the activity of osteoclasts in organ culture, J. Cell Biol. 60: 346.CrossRefGoogle Scholar
  35. Holtzer, H., Sanger, J., Ishikawa, H., and Strahxi, K., 1973, Selected topics in myogenesis, Cold Spring Harbor Symp. Quant. Biol. 37: 549.CrossRefGoogle Scholar
  36. Holtzer, H., Croop, J., Dienstman, S., and Somlyo, A. P., 1975, Effects of cytochalasin and colcemid on myogenic cultures, Proc. Natl. Acad Sci. U.S.A. 72: 513.CrossRefGoogle Scholar
  37. Hubbard, B. D., and Lazarides, E., 1979, Copurification of actin and desmin from chicken smooth muscle and their copolymerization in vitro to intermediate filaments, J. Cell Biol. 80: 166.CrossRefGoogle Scholar
  38. Inoué, S., and Ritter, H., Jr., 1975, Dynamics of mitotic spindle organization and function, in: Molecules and Cell Movements ( S. Inoue and R. E. Stephens, eds.), pp. 3–30, Raven Press, New York.Google Scholar
  39. Ishikawa, H., Bischoff, R., and Holtzer, H., 1968, Mitosis and intermediate-sized filaments in developing skeletal muscle, J. Cell Biol. 38: 538.CrossRefGoogle Scholar
  40. Ishikawa, H., Bischoff, R., and Holtzer, H., 1969, Formation of arrowhead complexes with heavy meromyosin in a variety of cell types, J. Cell Biol. 43: 312.CrossRefGoogle Scholar
  41. Izant, J. G., and Lazarides, E., 1974, Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis, Proc. Natl. Acad. Sci. U.S.A. 74: 1450.CrossRefGoogle Scholar
  42. Jacobus, W. E., and Lehninger, A. L., 1973, Creatine kinase of rat heart mitochondria, J. Biol. Chem. 248: 4803.Google Scholar
  43. Kelly, D. E., 1969, Myofibrillogenesis and Z-band differentiation, Anat. Rec. 163:403.CrossRefGoogle Scholar
  44. Knappeis, G. G., and Carlsen, F., 1962, The ultrastructure of the Z disc in skeletal muscle, J. Cell Biol. 13: 323.CrossRefGoogle Scholar
  45. Lazarides, E., 1978a, The distribution of desmin (100 A) filaments in primary cultures of embryonic chick cardiac cells, Exp. Cell Res. 112: 265.CrossRefGoogle Scholar
  46. Lazarides, E., 1978b, Comparison of the structure, distribution and possible function of desmin (100 A) filaments in various types of muscle and non muscle cells, Birth Defects Orig. Artic. Ser. 14: 41.Google Scholar
  47. Lazarides, E., 1980, Intermediate filaments as mechanical integrators of cellular space, Nature (London 283: 249.CrossRefGoogle Scholar
  48. Lazarides, E., and Balzer, D. R., Jr., 1978, Specificity of desmin to avian and mammalian cells, Cell 14: 429.CrossRefGoogle Scholar
  49. Lazarides, E., and Granger, B. L., 1978, Fluorescent localization of membrane sites in glycerinated chicken skeletal muscle fibers and the relationship of these sites to the protein composition of the Z disk, Proc. Natl. Acad. Sci. U.S.A. 75: 3683.CrossRefGoogle Scholar
  50. Lazarides, E., and Hubbard, B. D., 1976, Immunological characterization of the subunit of the 100 A filaments from muscle cells, Proc. Natl. Acad. Sci. U.S.A. 73: 4344.CrossRefGoogle Scholar
  51. Lazarides, E., and Revel, J. P., 1979, The molecular basis of cell movement, Sci. Am. 240: 100.CrossRefGoogle Scholar
  52. Lazarides, E., and Weber, K., 1974, Actin antibody: The specific visualization of actin filaments in non-muscle cells, Proc. Natl. Acad. Sci. U.S.A. 71: 2268.CrossRefGoogle Scholar
  53. Liem, R. K. H., Yen, S.-H., Salomon, G. D., and Shelanski, M. L., 1978, Intermediate filaments in nervous tissue, J. Cell Biol. 79: 637.CrossRefGoogle Scholar
  54. McEwen, B. S., and Grafstein, B., 1968, Fast and slow components in axonal transport of protein, J. Cell Biol. 38: 494.CrossRefGoogle Scholar
  55. Miller, C. L., Fuseler, J. W., and Brinkley, B. R., 1977, Cytoplasmic microtubules in transformed mouse x nontransformed human cell hybrids: Correlation with in vitro growth, Cell 12: 319.CrossRefGoogle Scholar
  56. Morris, G. F., Cooke, A., and Cole, R. J., 1972, Isoenzymes of creatine phosphokinase during myogenesis in vitro, Exp. Cell. Res. 74: 582.CrossRefGoogle Scholar
  57. Nandy, K., and Bourne, G. H., 1963, A study of the morphology of the conducting tissue in mammalian hearts, Acta Anat. 53: 217.CrossRefGoogle Scholar
  58. Nath, K., Shay, J. W., and Bollon, A. P., 1978, Relationship between dibutyryl cyclic AMP and microtubule organization in contracting heart muscle cells, Proc. Natl. Acad. Sci. U.S.A. 75: 319.CrossRefGoogle Scholar
  59. Ochs, S., 1972, Fast transport of materials in mammalian nerve fibers, Science 176: 252.CrossRefGoogle Scholar
  60. O’Farrell, P. H., 1975, High resolution two-dimensional electrophoresis of proteins, J. Biol. Chem. 250: 4007.Google Scholar
  61. Olden, K., and Yamada, K. M., 1977, Direct detection of antigens in sodium dodecyl sulfatepolyacrylamide gels, Anal. Biochem. 78: 483.CrossRefGoogle Scholar
  62. Oliphant, L. W., and Loewen, R. D., 1976, Filament systems in Purkinje cells of the sheep heart: Possible alteration of myofibrillogenesis, J. Mol. Cell Cardiol. 8: 679.CrossRefGoogle Scholar
  63. Osborn, M., Franke, W., and Weber, K., 1980, Direct demonstration of the presence of two immunologically distinct intermediate sized filament systems in the same cell by double immunofluorescence microscopy, Exp. Cell Res. 125: 37.CrossRefGoogle Scholar
  64. Page, E., Power, B., Fozzard, H. A., and Meddoff, D. A., 1969, Sarcolemmal evaginations with knob-like or stalked projections in Purkinje fibers of the sheep’s heart, J. Ultrastruct. Res. 28: 288.CrossRefGoogle Scholar
  65. Pollard, T. D., and Werhing, R. R., 1974, Actin and myosin and cell movement, CRC Grit. Rev. Biochem. 2: 1.CrossRefGoogle Scholar
  66. Rash, J. E., Shay, J. W., and Besele, J. J., 1968, Urea extraction of Z bands, intercalated disks, and desmosomes, J. Ultrastruct. Res. 24: 181.CrossRefGoogle Scholar
  67. Rash, J. E., Biesele, J. J., and Gey, G. O., 1970, Three classes of filaments in cardiac differentiation, J. Ultrastruct. Res. 33: 408.CrossRefGoogle Scholar
  68. Salmon, E. D., 1975, Spindle microtubules: Thermodynamics of in vitro assembly and role in chromosome movement, Ann. N. Y. Acad. Sci. 253: 383.CrossRefGoogle Scholar
  69. Schlaepfer, W. W., 1977, Immunological and ultrastructural studies of neurofilaments isolated from rat peripheral nerve, J. Cell Biol. 74: 226.CrossRefGoogle Scholar
  70. Schlaepfer, W. W., and Lynch, R. G., 1977, Immunofluorescence studies of neurofilaments in the rat and human peripheral and central nervous systems, J. Cell Biol. 74: 241.CrossRefGoogle Scholar
  71. Schollmeyer, J. V., Furcht, L. T., Goll, D. E., Robson, R. M., and Stromer, M. H., 1976, Localization of contractile proteins in smooth muscle cells and in normal and transformed fibroblast, in: Cell Motility, Book A ( R. D. Goldman, T. D. Pollard, and J. Rosenbaum, eds.), p. 364. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  72. Sharov, V. G., Saks, V. A., Smirnov, U. S., and Chazov, E. I., 1977, An electron microscopic histochemical investigation of the localization of creatine phosphokinase in heart cells, Biochim. Biophys. Acta 468: 495.CrossRefGoogle Scholar
  73. Shelanski, M. L., and Liem, R. K. H., 1979, Neurofilaments, J. Neurochem. 33: 5.CrossRefGoogle Scholar
  74. Small, J. V., 1977, Contractile units in vertebrate smooth muscle cells, Nature (London) 249: 324.CrossRefGoogle Scholar
  75. Small, J. V., and Sobieszek, A., 1977, Studies on the function and composition of the 10 mm (100-A) filaments of vertebrate smooth muscle, J. Cell Sci. 23: 243.Google Scholar
  76. Somlyo, A. P., Devine, C. E., Somlyo, A. V., and Rice, R. V., 1973, Filament organization in vertebrate smooth muscle, Philos. Trans. R. Soc. London Ser. B 265: 223.CrossRefGoogle Scholar
  77. Stephens, R. E., 1975, High resolution SDS-polyacrylamide gel electrophoresis: Fluorescent visualization and electrophoretic elution-concentration of protein bands, Anal. Biochem. 65: 369.CrossRefGoogle Scholar
  78. Stephens, R. E., and Edds, K. T., 1976, Microtubules: Structure, chemistry, and function, Physiol. Rev. 56: 709.Google Scholar
  79. Stossel, T. P., 1978, Contractile proteins in cell structure and function, Annu. Rev. Med. 29: 427.CrossRefGoogle Scholar
  80. Strehler, E. E., Pilloni, G., Heizman, C. W., and Eppenberger, H. M., 1979, M-protein in chicken cardiac muscle, Exp. Cell Res. 124: 39.CrossRefGoogle Scholar
  81. Sun, T.-T., Shih, C., and Green, H., 1979, Keratin cytoskeletons in epithelial cells of internal organs, Proc. Natl. Acad. Sci. U.S.A. 76: 2813.CrossRefGoogle Scholar
  82. Thornell, L.-E., 1973, Evidence of an imbalance in the synthesis and degradation of myofibrillar proteins in rabbit Purkinje fibers: An electron microscope study, J. Ultrastruct. Res. 44: 85.CrossRefGoogle Scholar
  83. Thornell, L.-E., 1974, An ultrahistochemical study on glycogen in cow Purkinje fibers, J. Mol. Cell. Cardiol. 6: 439.CrossRefGoogle Scholar
  84. Turner, D. C., and Eppenberger, H. M., 1973, Developmental changes in creatine kinase and aldolase isoenzymes and their possible association with contractile elements, Enzyme (Basel) 15: 224.Google Scholar
  85. Tuszynski, B. P., Frank, E. D., Damsky, C. H., Buck, C., and Warren, L., 1979, The detection of smooth musde desmin-like protein in BHK21/C13 fibroblasts, J. Biol. Chem. 254: 6138.Google Scholar
  86. Uehara, Y., Campbell, G. R., and Burnstock, G., 1971, Cytoplasmic filaments in developing and adult vertbrate smooth muscle, J. Cell Biol. 50: 484.CrossRefGoogle Scholar
  87. Ullrick, W. C., Toselli, P. A., Saide J., and Phear, W. P. C., 1977, Fine structure of the Z-disc, J. Mol. Biol. 115: 61.CrossRefGoogle Scholar
  88. Viraǵh, S., and Chalice, C. E., 1969, Variations in filamentous and fibrillar organization, and associated sarcolemmal structures, in cells of the normal mammalian heart, J. Ultrastruct. Res. 28: 321.CrossRefGoogle Scholar
  89. Wallimann, I., Turner, D. C., and Eppenberger, H. M.. 1978a, Localization of creatine kinase isoenzyme in myofibrils. I. Chicken skeletal muscle, J. Cell Biol. 75: 297.CrossRefGoogle Scholar
  90. Wallimann, T. H., Kuhn, J., Pelloni, G., Turner, D. C., and Eppenberger, H. M., 1978b, Localization of creatine kinase isoenzyme in myofibrils. II. Chicken heart muscle, J. Cell Biol. 75: 318.CrossRefGoogle Scholar
  91. Wallimann, T., Pelloni, G., Turner, D. C., and Eppenberger, H. M., 1978c, Monovalent antibodies against MM-creatine kinase remove the M-line from myofibrils, Proc. Natl. Acad. Sci. U.S.A. 75: 4296.CrossRefGoogle Scholar
  92. Weiss, P. A., 1972a, Neuronal dynamics and axonal flow. V. The semisolid state of the moving axonal column, Proc. Natl. Acad. Sci. U.S.A. 69: 620.CrossRefGoogle Scholar
  93. Weiss, P. A., 1972b, Neuronal dynamics and axonal flow: Axonal peristalsis, Proc. Natl. Acad. Sci. U.S.A. 69: 1309.CrossRefGoogle Scholar
  94. Weiss, P. A., and Mayr, R., 1971, Organelles in neuroplasmic (“axonal”) flow: Neurofilaments, Proc. Natl. Acad. Sci. U.S.A. 68: 846.CrossRefGoogle Scholar
  95. Wesniewski, H., Shelanski, M. L., and Terry, R. D., 1968, Effect of mitotic spindle inhibitors on neurotubules and neurofilaments in anterior horn cells, J. Cell Biol. 38: 224.CrossRefGoogle Scholar
  96. Zackroff, R. V., and Goldman, R. D., 1979, In vitro assembly of intermediate filaments from baby hamster kidney (BHK-21) cells, Proc. Natl. Acad. Sci. U.S.A. 76: 6226.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • John W. Fuseler
    • 1
  • Jerry W. Shay
    • 1
  • Howard Feit
    • 2
  1. 1.Department of Cell BiologyThe University of Texas Health Science Center at DallasDallasUSA
  2. 2.Departments of Cell Biology and NeurologyThe University of Texas Health Science Center at DallasDallasUSA

Personalised recommendations