Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds

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Abstract

Intermediate filaments are cytoskeletal polymers encoded by a large family of differentially expressed genes that provide crucial structural support in the cytoplasm and nucleus of higher eukaryotes. Perturbation of their function accounts for several genetically determined diseases in which fragile cells cannot sustain mechanical and non-mechanical stresses. Recent studies shed light on how this structural support is modulated to meet the changing needs of cells, and reveal a novel role whereby intermediate filaments influence cell growth and death through dynamic interactions with non-structural proteins.

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Figure 1: Major cellular functions of cytoplasmic intermediate filaments.

References

  1. 1

    Lazarides, E. Intermediate filaments as mechanical integrators of cellular space. Nature 283, 249–256 (1980).

  2. 2

    Alberts, B. et al. Molecular Biology of the Cell, 4th Edition. 907–982 (Garland Science, New York, 2002).

  3. 3

    Coulombe, P.A., Ma, L., Yamada, S. & Wawersik, M. Intermediate filaments at a glance. J. Cell Sci. 114, 4345–4347 (2001).

  4. 4

    Hesse, M., Magin, T.M. & Weber, K. Genes for intermediate filament proteins and the draft sequence of the human genome: novel keratin genes and a surprisingly high number of pseudogenes related to keratin genes 8 and 18. J. Cell Sci. 114, 2569–2575 (2001).

  5. 5

    Erber, A. et al. Characterization of the Hydra lamin and its gene: A molecular phylogeny of metazoan lamins. J. Mol. Evol. 49, 260–271 (1999).

  6. 6

    Hutchison, C.J. Lamins: building blocks or regulators of gene expression? Nature Rev. Mol. Cell Biol. 3, 848–858 (2002).

  7. 7

    Gruenbaum, Y. et al. The nuclear lamina and its functions in the nucleus. Int. Rev. Cytol. 226, 1–62 (2003).

  8. 8

    Fuchs, E. & Weber, K. Intermediate filaments: structure, dynamics, function, and disease. Annu. Rev. Biochem. 63, 345–382 (1994).

  9. 9

    Fuchs, E. & Cleveland, D.W. A structural scaffolding of intermediate filaments in health and disease. Science 279, 514–519 (1998).

  10. 10

    Strelkov, S.V., Herrmann, H. & Aebi, U. Molecular architecture of intermediate filaments. Bioessays 25, 243–251 (2003).

  11. 11

    Herrmann, H., Hesse, M., Reichenzeller, M., Aebi, U. & Magin, T.M. Functional complexity of intermediate filament cytoskeletons: from structure to assembly to gene ablation. Int. Rev. Cytol. 223, 83–175 (2003).

  12. 12

    Er Rafik, M., Doucet, J. & Briki, F. The intermediate filament architecture as determined by X-Ray diffraction modeling of hard alpha-keratin. Biophys. J. 86, 3893–3904 (2004).

  13. 13

    Windoffer, R., Woll, S., Strnad, P. & Leube, R.E. Identification of novel principles of keratin filament network turnover in living cells. Mol. Biol. Cell 15, 2436–2448 (2004).

  14. 14

    Vassar, R., Coulombe, P.A., Degenstein, L., Albers, K. & Fuchs, E. Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease. Cell 64, 365–380 (1991).

  15. 15

    Fuchs, E., Esteves, R.A. & Coulombe, P.A. Transgenic mice expressing a mutant keratin 10 gene reveal the likely genetic basis for epidermolytic hyperkeratosis. Proc. Natl Acad. Sci. USA 89, 6906–6910 (1992).

  16. 16

    Omary, M.B., Coulombe, P.A. & McLean, W.H.I. Intermediate filaments and their associate diseases. N. Engl. J. Med. (In the press).

  17. 17

    Novelli, G. & D'Apice, M.R. The strange case of the “lumper” lamin A/C gene and human premature ageing. Trends Mol. Med. 9, 370–375 (2003).

  18. 18

    Worman, H.J. & Courvalin, J.C. How do mutations in lamins A and C cause disease? J. Clin. Invest. 113, 349–351 (2004).

  19. 19

    Zastrow, M.S., Vlcek, S. & Wilson, K.L. Proteins that bind A-type lamins: integrating isolated clues. J. Cell Sci. 117, 979–987 (2004).

  20. 20

    Coulombe, P.A., Bousquet, O., Ma, L., Yamada, S. & Wirtz, D. The 'ins' and 'outs' of intermediate filament organization. Trends Cell Biol. 10, 420–428 (2000).

  21. 21

    Green, K.J. & Gaudry, C.A. Are desmosomes more than tethers for intermediate filaments? Nature Rev. Mol. Cell Biol. 1, 208–216 (2000).

  22. 22

    Fuchs, E. & Karakesisoglou, I. Bridging cytoskeletal intersections. Genes Dev. 15, 1–14 (2001).

  23. 23

    Leung, C.L., Green, K.J. & Liem, R.K. Plakins: a family of versatile cytolinker proteins. Trends Cell Biol. 12, 37–45 (2002).

  24. 24

    Roper, K., Gregory, S.L. & Brown, N.H. The 'spectraplakins': cytoskeletal giants with characteristics of both spectrin and plakin families. J. Cell Sci. 115, 4215–4225 (2002).

  25. 25

    Coulombe, P.A. & Omary, M.B. 'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments. Curr. Opin. Cell Biol. 14, 110–122 (2002).

  26. 26

    Mounkes, L., Kozlov, S., Burke, B. & Stewart, C.L. The laminopathies: nuclear structure meets disease. Curr. Opin. Genet. Dev. 13, 223–230 (2003).

  27. 27

    Erber, A., Riemer, D., Bovenschulte, M. & Weber, K. Molecular phylogeny of metazoan intermediate filament proteins. J. Mol. Evol. 47, 751–762 (1998).

  28. 28

    Karabinos, A., Schmidt, H., Harborth, J., Schnabel, R. & Weber, K. Essential roles for four cytoplasmic intermediate filament proteins in Caenorhabditis elegans development. Proc. Natl Acad. Sci. USA 98, 7863–7868 (2001).

  29. 29

    Ausmees, N., Kuhn, J.R. & Jacobs-Wagner, C. The bacterial cytoskeleton: an intermediate filament-like function in cell shape. Cell 115, 705–713 (2003).

  30. 30

    van den Ent, F., Amos, L.A. & Lowe, J. Prokaryotic origin of the actin cytoskeleton. Nature 413, 39–44 (2001).

  31. 31

    Lowe, J. & Amos, L.A. Crystal structure of the bacterial cell-division protein FtsZ. Nature 391, 203–206 (1998).

  32. 32

    Lariviere, R.C. & Julien, J.P. Functions of intermediate filaments in neuronal development and disease. J. Neurobiol. 58, 131–148 (2004).

  33. 33

    McConnell, S.J. & Yaffe, M.P. Intermediate filament formation by a yeast protein essential for organelle inheritance. Science 260, 687–689 (1993).

  34. 34

    Omary, M.B., Ku, N.O. & Toivola, D.M. Keratins: guardians of the liver. Hepatology 35, 251–257 (2002).

  35. 35

    Oshima, R.G. Apoptosis and keratin intermediate filaments. Cell Death Differ. 9, 486–492 (2002).

  36. 36

    Paramio, J.M. & Jorcano, J.L. Beyond structure: do intermediate filaments modulate cell signalling? Bioessays 24, 836–844 (2002).

  37. 37

    Owens, D.W. & Lane, E.B. The quest for the function of simple epithelial keratins. Bioessays 25, 748–758 (2003).

  38. 38

    Baribault, H., Price, J., Miyai, K. & Oshima, R.G. Mid-gestational lethality in mice lacking keratin 8. Genes Dev. 7, 1191–1202 (1993).

  39. 39

    Ku, N.O., Michie, S., Oshima, R.G. & Omary, M.B. Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mutant. J. Cell Biol. 131, 1303–1314 (1995).

  40. 40

    Loranger, A. et al. Simple epithelium keratins are required for maintenance of hepatocyte integrity. Am. J. Pathol. 151, 1673–1683 (1997).

  41. 41

    Magin, T.M. et al. Lessons from keratin 18 knockout mice: formation of novel keratin filaments, secondary loss of keratin 7 and accumulation of liver-specific keratin 8-positive aggregates. J. Cell Biol. 140, 1441–1451 (1998).

  42. 42

    Ku, N.O. et al. Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human keratin 18 mutant. J. Clin. Invest. 98, 1034–1046 (1996).

  43. 43

    Toivola, D.M. et al. Protein phosphatase inhibition in normal and keratin 8/18 assembly-incompetent mouse strains supports a functional role of keratin intermediate filaments in preserving hepatocyte integrity. Hepatology 28, 116–128 (1998).

  44. 44

    Zatloukal, K. et al. Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies. Am. J. Pathol. 156, 1263–1274 (2000).

  45. 45

    Ku, N.O. et al. Mutation of a major keratin phosphorylation site predisposes to hepatotoxic injury in transgenic mice. J. Cell Biol. 143, 2023–2032 (1998).

  46. 46

    Liao, J., Lowthert, L.A., Ghori, N. & Omary, M.B. The 70-kDa heat shock proteins associate with glandular intermediate filaments in an ATP-dependent manner. J. Biol. Chem. 270, 915–922 (1995).

  47. 47

    Izawa, I. et al. Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein. J. Biol. Chem. 275, 34521–34527 (2000).

  48. 48

    Perng, M.D. et al. Intermediate filament interactions can be altered by HSP27 and αB-crystallin. J. Cell Sci. 112, 2099–2112 (1999).

  49. 49

    Omary, M.B. et al. PKCε-related kinase associates with and phosphorylates cytokeratin 8 and 18. J. Cell Biol. 117, 583–593 (1992).

  50. 50

    He, T., Stepulak, A., Holmstrom, T.H., Omary, M.B. & Eriksson, J.E. The intermediate filament protein keratin 8 is a novel cytoplasmic substrate for c-Jun N-terminal kinase. J. Biol. Chem. 277, 10767–10774 (2002).

  51. 51

    Ku, N.O., Gish, R., Wright, T.L. & Omary, M.B. Keratin 8 mutations in patients with cryptogenic liver disease. N. Engl. J. Med. 344, 1580–1587 (2001).

  52. 52

    Ku, N.O. et al. Keratin 8 and 18 mutations are risk factors for developing liver disease of multiple etiologies. Proc. Natl Acad. Sci. USA 100, 6063–6068 (2003).

  53. 53

    Owens, D.W. et al. Human keratin 8 mutations that disturb filament assembly observed in inflammatory bowel disease patients. J. Cell Sci. 117, 1989–1999 (2004).

  54. 54

    Caulin, C., Ware, C.F., Magin, T.M. & Oshima, R.G. Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. J. Cell Biol. 149, 17–22 (2000).

  55. 55

    Gilbert, S., Loranger, A., Daigle, N. & Marceau, N. Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. J. Cell Biol. 154, 763–773 (2001).

  56. 56

    Inada, H. et al. Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD. J. Cell Biol. 155, 415–426 (2001).

  57. 57

    Ku, N.O., Soetikno, R.M. & Omary, M.B. Keratin mutation in transgenic mice predisposes to Fas but not TNF-induced apoptosis and massive liver injury. Hepatology 37, 1006–1014 (2003).

  58. 58

    Jaquemar, D. et al. Keratin 8 protection of placental barrier function. J. Cell Biol. 161, 749–756 (2003).

  59. 59

    McGowan, K.M. et al. Keratin 17 null mice exhibit age- and strain-dependent alopecia. Genes Dev. 16, 1412–1422 (2002).

  60. 60

    Hardy, M.H. The secret life of the hair follicle. Trends Genet. 8, 55–61 (1992).

  61. 61

    Robertson, J. et al. Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factor-α. J. Cell Biol. 155, 217–226 (2001).

  62. 62

    Hesse, M., Franz, T., Tamai, Y., Taketo, M.M. & Magin, T.M. Targeted deletion of keratins 18 and 19 leads to trophoblast fragility and early embryonic lethality. EMBO J. 19, 5060–5070 (2000).

  63. 63

    Ameen, N.A., Figueroa, Y. & Salas, P.J. Anomalous apical plasma membrane phenotype in CK8-deficient mice indicates a novel role for intermediate filaments in the polarization of simple epithelia. J. Cell Sci. 114, 563–575 (2001).

  64. 64

    Toivola, D.M., Krishnan, S., Binder, H.J., Singh, S.K. & Omary, M.B. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J. Cell Biol. 164, 911–921 (2004).

  65. 65

    Micheau, O. & Tschopp, J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114, 181–190 (2003).

  66. 66

    Yoneda, K. et al. An autocrine/paracrine loop linking keratin 14 aggregates to tumor necrosis factor α-mediated cytotoxicity in a keratinocyte model of epidermolysis bullosa simplex. J. Biol. Chem. 279, 7296–7303 (2004).

  67. 67

    Sahlgren, C.M. et al. Cdk5 regulates the organization of Nestin and its association with p35. Mol. Cell. Biol. 23, 5090–5106 (2003).

  68. 68

    Lee, J.C. et al. DEDD regulates degradation of intermediate filaments during apoptosis. J. Cell Biol. 158, 1051–1066 (2002).

  69. 69

    Dinsdale, D., Lee, J.C., Dewson, G., Cohen, G.M. & Peter, M.E. Intermediate filaments control the intracellular distribution of caspases during apoptosis. Am. J. Pathol. 164, 395–407 (2004).

  70. 70

    Rao, L., Perez, D. & White, E. Lamin proteolysis facilitates nuclear events during apoptosis. J. Cell Biol. 135, 1441–1455 (1996).

  71. 71

    Broers, J.L. et al. Partial cleavage of A-type lamins concurs with their total disintegration from the nuclear lamina during apoptosis. Eur. J. Cell Biol. 81, 677–691 (2002).

  72. 72

    Ruchaud, S. et al. Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation. EMBO J. 21, 1967–1977 (2002).

  73. 73

    Byun, Y. et al. Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Differ. 8, 443–450 (2001).

  74. 74

    Chen, F., Chang, R., Trivedi, M., Capetanaki, Y. & Cryns, V.L. Caspase proteolysis of desmin produces a dominant-negative inhibitor of intermediate filaments and promotes apoptosis. J. Biol. Chem. 278, 6848–6853 (2003).

  75. 75

    Caulin, C., Salvesen, G.S. & Oshima, R.G. Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. J. Cell Biol. 138, 1379–1394 (1997).

  76. 76

    Ku, N.O., Liao, J. & Omary, M.B. Apoptosis generates stable fragments of human type I keratins. J. Biol. Chem. 272, 33197–33203 (1997).

  77. 77

    Ueno, T. et al. Measurement of an apoptotic product in the sera of breast cancer patients. Eur. J. Cancer 39, 769–774 (2003).

  78. 78

    Eriksson, J.E., Opal, P. & Goldman, R.D. Intermediate filament dynamics. Curr. Opin. Cell. Biol. 4, 99–104 (1992).

  79. 79

    Inagaki, M. et al. Dynamic properties of intermediate filaments: Regulation by phosphorylation. Bioessays 18, 481–487 (1996).

  80. 80

    Foisner, R. Dynamic organisation of intermediate filaments and associated proteins during the cell cycle. Bioessays 19, 297–305 (1997).

  81. 81

    Paramio, J.M., Segrelles, C., Ruiz, S. & Jorcano, J.L. Inhibition of protein kinase B (PKB) and PKCζ mediates keratin K10-induced cell cycle arrest. Mol. Cell. Biol. 21, 7449–7459 (2001).

  82. 82

    Paramio, J.M. et al. Modulation of cell proliferation by cytokeratins K10 and K16. Mol. Cell. Biol. 19, 3086–3094 (1999).

  83. 83

    Santos, M., Paramio, J.M., Bravo, A., Ramirez, A. & Jorcano, J.L. The expression of keratin k10 in the basal layer of the epidermis inhibits cell proliferation and prevents skin tumorigenesis. J. Biol. Chem. 277, 19122–19130 (2002).

  84. 84

    Santos, M. et al. Impaired NF-κB activation and increased production of tumor necrosis factor α in transgenic mice expressing keratin K10 in the basal layer of the epidermis. J. Biol. Chem. 278, 13422–13430 (2003).

  85. 85

    Reichelt, J. & Magin, T.M. Hyperproliferation, induction of c-Myc and 14-3-3σ, but no cell fragility in keratin-10-null mice. J. Cell Sci. 115, 2639–2650 (2002).

  86. 86

    Reichelt, J., Bussow, H., Grund, C. & Magin, T.M. Formation of a normal epidermis supported by increased stability of keratins 5 and 14 in keratin 10 null mice. Mol. Biol. Cell 12, 1557–1568 (2001).

  87. 87

    Schweizer, J., Kinjo, M., Furstenberger, G. & Winter, H. Sequential expression of mRNA-encoded keratin sets in neonatal mouse epidermis: basal cells with properties of terminally differentiating cells. Cell 37, 159–170 (1984).

  88. 88

    Toivola, D.M. et al. Disturbances in hepatic cell-cycle regulation in mice with assembly-deficient keratins 8/18. Hepatology 34, 1174–1183 (2001).

  89. 89

    Ku, N.O., Liao, J. & Omary, M.B. Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3 proteins. EMBO J. 17, 1892–1906 (1998).

  90. 90

    Hermeking, H. The 14-3-3 cancer connection. Nature Rev. Cancer 3, 931–943 (2003).

  91. 91

    Ku, N.O., Michie, S., Resurreccion, E.Z., Broome, R.L. & Omary, M.B. Keratin binding to 14-3-3 proteins modulates keratin filaments and hepatocyte mitotic progression. Proc. Natl Acad. Sci. USA 99, 4373–4378 (2002).

  92. 92

    Tzivion, G., Luo, Z.J. & Avruch, J. Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo. J. Biol. Chem. 275, 29772–26778 (2000).

  93. 93

    Martin, P. Wound healing — aiming for perfect skin regeneration. Science 276, 75–81 (1997).

  94. 94

    Wong, P. & Coulombe, P.A. Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repair. J. Cell Biol. 163, 327–337 (2003).

  95. 95

    Pekny, M. et al. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J. Cell Biol. 145, 503–514 (1999).

  96. 96

    Odland, G. & Ross, R. Human wound repair. I. Epidermal regeneration. J. Cell Biol. 39, 135–151 (1968).

  97. 97

    Paladini, R.D., Takahashi, K., Bravo, N.S. & Coulombe, P.A. Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16. J. Cell Biol. 132, 381–397 (1996).

  98. 98

    Mansbridge, J.N. & Knapp, A.M. Changes in keratinocyte maturation during wound healing. J. Invest. Dermatol. 89, 253–263 (1987).

  99. 99

    Wong, P. et al. Introducing a null mutation in the mouse K6α and K6β genes reveals their essential structural role in the oral mucosa. J. Cell Biol. 150, 921–928 (2000).

  100. 100

    Wojcik, S.M., Longley, M.A. & Roop, D.R. Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b. J. Cell Biol. 154, 619–630 (2001).

  101. 101

    Cozzolino, M. et al. p120 Catenin is required for growth factor-dependent cell motility and scattering in epithelial cells. Mol. Biol. Cell 14, 1964–1977 (2003).

  102. 102

    Mazzalupo, S., Wong, P., Martin, P. & Coulombe, P.A. Role for keratins 6 and 17 during wound closure in embryonic mouse skin. Dev. Dyn. 226, 356–365 (2003).

  103. 103

    Beil, M. et al. Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nature Cell Biol. 5, 803–811 (2003).

  104. 104

    Morley, S.M. et al. Generation and characterization of epidermolysis bullosa simplex cell lines: scratch assays show faster migration with disruptive keratin mutations. Br. J. Dermatol. 149, 46–58 (2003).

  105. 105

    Janmey, P.A., Euteneuer, U., Traub, P. & Schliwa, M. Viscoelastic properties of vimentin compared with other filamentous biopolymer networks. J. Cell Biol. 113, 155–160 (1991).

  106. 106

    Yamada, S., Wirtz, D. & Coulombe, P.A. Pairwise assembly determines the intrinsic potential for self-organization and mechanical properties of keratin filaments. Mol. Biol. Cell 13, 382–391 (2002).

  107. 107

    Ma, L., Yamada, S., Wirtz, D. & Coulombe, P.A. A 'hot-spot' mutation alters the mechanical properties of keratin filament networks. Nature Cell Biol. 3, 503–506 (2001).

  108. 108

    Brown, M.J., Hallam, J.A., Colucci-Guyon, E. & Shaw, S. Rigidity of circulating lymphocytes is primarily conferred by vimentin intermediate filaments. J. Immunol. 166, 6640–6646 (2001).

  109. 109

    Brown, M.J., Hallam, J.A., Liu, Y., Yamada, K.M. & Shaw, S. Cutting edge: integration of human T lymphocyte cytoskeleton by the cytolinker plectin. J. Immunol. 167, 641–645 (2001).

  110. 110

    Wiche, G. Role of plectin in cytoskeleton organization and dynamics. J. Cell Sci. 111, 2477–2486 (1998).

  111. 111

    Runembert, I. et al. Vimentin affects localization and activity of sodium-glucose cotransporter SGLT1 in membrane rafts. J. Cell Sci. 115, 713–724 (2002).

  112. 112

    Mor-Vaknin, N., Punturieri, A., Sitwala, K. & Markovitz, D.M. Vimentin is secreted by activated macrophages. Nature Cell Biol. 5, 59–63 (2003).

  113. 113

    Milner, D.J., Mavroidis, M., Weisleder, N. & Capetanaki, Y. Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J. Cell Biol. 150, 1283–1298 (2000).

  114. 114

    Linden, M., Li, Z., Paulin, D., Gotow, T. & Leterrier, J.F. Effects of desmin gene knockout on mice heart mitochondria. J. Bioenerg. Biomembr. 33, 333–341 (2001).

  115. 115

    Weisleder, N., Taffet, G.E. & Capetanaki, Y. Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc. Natl Acad. Sci. USA 101, 769–774 (2004).

  116. 116

    Rao, M.V. et al. Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J. Cell Biol. 159, 279–290 (2002).

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Acknowledgements

The authors thank C. Parent, B. Omary, and C. Jacobs-Wagner for their comments and members of the laboratory for their support. This effort was supported by grants AR42047 and AR44232 from the National Institutes of Health to P.A.C.

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Correspondence to Pauline Wong.

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Coulombe, P., Wong, P. Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nat Cell Biol 6, 699–706 (2004) doi:10.1038/ncb0804-699

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