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. 1994 Jul 2;126(2):445–456. doi: 10.1083/jcb.126.2.445

Differential organization of desmin and vimentin in muscle is due to differences in their head domains

PMCID: PMC2200016  PMID: 7518466

Abstract

In most myogenic systems, synthesis of the intermediate filament (IF) protein vimentin precedes the synthesis of the muscle-specific IF protein desmin. In the dorsal myotome of the Xenopus embryo, however, there is no preexisting vimentin filament system and desmin's initial organization is quite different from that seen in vimentin-containing myocytes (Cary and Klymkowsky, 1994. Differentiation. In press.). To determine whether the organization of IFs in the Xenopus myotome reflects features unique to Xenopus or is due to specific properties of desmin, we used the injection of plasmid DNA to drive the synthesis of vimentin or desmin in myotomal cells. At low levels of accumulation, exogenous vimentin and desmin both enter into the endogenous desmin system of the myotomal cell. At higher levels exogenous vimentin forms longitudinal IF systems similar to those seen in vimentin-expressing myogenic systems and massive IF bundles. Exogenous desmin, on the other hand, formed a reticular IF meshwork and non-filamentous aggregates. In embryonic epithelial cells, both vimentin and desmin formed extended IF networks. Vimentin and desmin differ most dramatically in their NH2- terminal "head" regions. To determine whether the head region was responsible for the differences in the behavior of these two proteins, we constructed plasmids encoding chimeric proteins in which the head of one was attached to the body of the other. In muscle, the vimentin head- desmin body (VDD) polypeptide formed longitudinal IFs and massive IF bundles like vimentin. The desmin head-vimentin body (DVV) polypeptide, on the other hand, formed IF meshworks and non-filamentous structures like desmin. In embryonic epithelial cells DVV formed a discrete filament network while VDD did not. Based on the behavior of these chimeric proteins, we conclude that the head domains of vimentin and desmin are structurally distinct and not interchangeable, and that the head domain of desmin is largely responsible for desmin's muscle- specific behaviors.

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Selected References

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  1. Bennett G. S., Fellini S. A., Toyama Y., Holtzer H. Redistribution of intermediate filament subunits during skeletal myogenesis and maturation in vitro. J Cell Biol. 1979 Aug;82(2):577–584. doi: 10.1083/jcb.82.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blessing M., Rüther U., Franke W. W. Ectopic synthesis of epidermal cytokeratins in pancreatic islet cells of transgenic mice interferes with cytoskeletal order and insulin production. J Cell Biol. 1993 Feb;120(3):743–755. doi: 10.1083/jcb.120.3.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brady A. J. Passive stiffness of rat cardiac myocytes. J Biomech Eng. 1984 Feb;106(1):25–30. doi: 10.1115/1.3138451. [DOI] [PubMed] [Google Scholar]
  4. Capetanaki Y., Smith S., Heath J. P. Overexpression of the vimentin gene in transgenic mice inhibits normal lens cell differentiation. J Cell Biol. 1989 Oct;109(4 Pt 1):1653–1664. doi: 10.1083/jcb.109.4.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cary R. B., Klymkowsky M. W. Desmin organization during the differentiation of the dorsal myotome in Xenopus laevis. Differentiation. 1994 Apr;56(1-2):31–38. doi: 10.1046/j.1432-0436.1994.56120031.x. [DOI] [PubMed] [Google Scholar]
  6. Ching G. Y., Liem R. K. Assembly of type IV neuronal intermediate filaments in nonneuronal cells in the absence of preexisting cytoplasmic intermediate filaments. J Cell Biol. 1993 Sep;122(6):1323–1335. doi: 10.1083/jcb.122.6.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Christian J. L., Edelstein N. G., Moon R. T. Overexpression of wild-type and dominant negative mutant vimentin subunits in developing Xenopus embryos. New Biol. 1990 Aug;2(8):700–711. [PubMed] [Google Scholar]
  8. Cossette L. J., Vincent M. Expression of a developmentally regulated cross-linking intermediate filament-associated protein (IFAPa-400) during the replacement of vimentin for desmin in muscle cell differentiation. J Cell Sci. 1991 Feb;98(Pt 2):251–260. doi: 10.1242/jcs.98.2.251. [DOI] [PubMed] [Google Scholar]
  9. Craig S. W., Pardo J. V. Gamma actin, spectrin, and intermediate filament proteins colocalize with vinculin at costameres, myofibril-to-sarcolemma attachment sites. Cell Motil. 1983;3(5-6):449–462. doi: 10.1002/cm.970030513. [DOI] [PubMed] [Google Scholar]
  10. Cross G. S., Wilson C., Erba H. P., Woodland H. R. Cytoskeletal actin gene families of Xenopus borealis and Xenopus laevis. J Mol Evol. 1988;27(1):17–28. doi: 10.1007/BF02099726. [DOI] [PubMed] [Google Scholar]
  11. Côté F., Collard J. F., Julien J. P. Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell. 1993 Apr 9;73(1):35–46. doi: 10.1016/0092-8674(93)90158-m. [DOI] [PubMed] [Google Scholar]
  12. D'Amati G., Kahn H. J., Butany J., Silver M. D. Altered distribution of desmin filaments in hypertrophic cardiomyopathy: an immunohistochemical study. Mod Pathol. 1992 Mar;5(2):165–168. [PubMed] [Google Scholar]
  13. Dent J. A., Cary R. B., Bachant J. B., Domingo A., Klymkowsky M. W. Host cell factors controlling vimentin organization in the Xenopus oocyte. J Cell Biol. 1992 Nov;119(4):855–866. doi: 10.1083/jcb.119.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dent J. A., Polson A. G., Klymkowsky M. W. A whole-mount immunocytochemical analysis of the expression of the intermediate filament protein vimentin in Xenopus. Development. 1989 Jan;105(1):61–74. doi: 10.1242/dev.105.1.61. [DOI] [PubMed] [Google Scholar]
  15. Dunia I., Pieper F., Manenti S., van de Kemp A., Devilliers G., Benedetti E. L., Bloemendal H. Plasma membrane-cytoskeleton damage in eye lenses of transgenic mice expressing desmin. Eur J Cell Biol. 1990 Oct;53(1):59–74. [PubMed] [Google Scholar]
  16. Edström L., Thornell L. E., Eriksson A. A new type of hereditary distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. J Neurol Sci. 1980 Aug;47(2):171–190. doi: 10.1016/0022-510x(80)90002-7. [DOI] [PubMed] [Google Scholar]
  17. Evans R. M. The intermediate-filament proteins vimentin and desmin are phosphorylated in specific domains. Eur J Cell Biol. 1988 Apr;46(1):152–160. [PubMed] [Google Scholar]
  18. Eyer J., Peterson A. Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein. Neuron. 1994 Feb;12(2):389–405. doi: 10.1016/0896-6273(94)90280-1. [DOI] [PubMed] [Google Scholar]
  19. Fidzianska A., Goebel H. H., Osborn M., Lenard H. G., Osse G., Langenbeck U. Mallory body-like inclusions in a hereditary congenital neuromuscular disease. Muscle Nerve. 1983 Mar-Apr;6(3):195–200. doi: 10.1002/mus.880060305. [DOI] [PubMed] [Google Scholar]
  20. Gard D. L., Lazarides E. The synthesis and distribution of desmin and vimentin during myogenesis in vitro. Cell. 1980 Jan;19(1):263–275. doi: 10.1016/0092-8674(80)90408-0. [DOI] [PubMed] [Google Scholar]
  21. Geisler N., Hatzfeld M., Weber K. Phosphorylation in vitro of vimentin by protein kinases A and C is restricted to the head domain. Identification of the phosphoserine sites and their influence on filament formation. Eur J Biochem. 1989 Aug 1;183(2):441–447. doi: 10.1111/j.1432-1033.1989.tb14947.x. [DOI] [PubMed] [Google Scholar]
  22. Geisler N., Weber K. Phosphorylation of desmin in vitro inhibits formation of intermediate filaments; identification of three kinase A sites in the aminoterminal head domain. EMBO J. 1988 Jan;7(1):15–20. doi: 10.1002/j.1460-2075.1988.tb02778.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gill S. R., Wong P. C., Monteiro M. J., Cleveland D. W. Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit. J Cell Biol. 1990 Nov;111(5 Pt 1):2005–2019. doi: 10.1083/jcb.111.5.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Goebel H. H., Bornemann A. Desmin pathology in neuromuscular diseases. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;64(3):127–135. doi: 10.1007/BF02915105. [DOI] [PubMed] [Google Scholar]
  25. Granger B. L., Lazarides E. Desmin and vimentin coexist at the periphery of the myofibril Z disc. Cell. 1979 Dec;18(4):1053–1063. doi: 10.1016/0092-8674(79)90218-6. [DOI] [PubMed] [Google Scholar]
  26. Halbig L., Goebel H. H., Hopf H. C., Moll R. Spheroid-cytoplasmic complexes in a congenital myopathy. Rev Neurol (Paris) 1991;147(4):300–307. [PubMed] [Google Scholar]
  27. Hemsley A., Arnheim N., Toney M. D., Cortopassi G., Galas D. J. A simple method for site-directed mutagenesis using the polymerase chain reaction. Nucleic Acids Res. 1989 Aug 25;17(16):6545–6551. doi: 10.1093/nar/17.16.6545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Herrmann H., Eckelt A., Brettel M., Grund C., Franke W. W. Temperature-sensitive intermediate filament assembly. Alternative structures of Xenopus laevis vimentin in vitro and in vivo. J Mol Biol. 1993 Nov 5;234(1):99–113. doi: 10.1006/jmbi.1993.1566. [DOI] [PubMed] [Google Scholar]
  29. Herrmann H., Fouquet B., Franke W. W. Expression of intermediate filament proteins during development of Xenopus laevis. I. cDNA clones encoding different forms of vimentin. Development. 1989 Feb;105(2):279–298. doi: 10.1242/dev.105.2.279. [DOI] [PubMed] [Google Scholar]
  30. Herrmann H., Fouquet B., Franke W. W. Expression of intermediate filament proteins during development of Xenopus laevis. II. Identification and molecular characterization of desmin. Development. 1989 Feb;105(2):299–307. doi: 10.1242/dev.105.2.299. [DOI] [PubMed] [Google Scholar]
  31. Hoffmann W., Franz J. K., Franke W. W. Amino acid sequence microheterogeneities of basic (type II) cytokeratins of Xenopus laevis epidermis and evolutionary conservativity of helical and non-helical domains. J Mol Biol. 1985 Aug 20;184(4):713–724. doi: 10.1016/0022-2836(85)90315-8. [DOI] [PubMed] [Google Scholar]
  32. Holtzer H., Bennett G. S., Tapscott S. J., Croop J. M., Toyama Y. Intermediate-size filaments: changes in synthesis and distribution in cells of the myogenic and neurogenic lineages. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 1):317–329. doi: 10.1101/sqb.1982.046.01.033. [DOI] [PubMed] [Google Scholar]
  33. Klymkowsky M. W., Hanken J. Whole-mount staining of Xenopus and other vertebrates. Methods Cell Biol. 1991;36:419–441. doi: 10.1016/s0091-679x(08)60290-3. [DOI] [PubMed] [Google Scholar]
  34. Klymkowsky M. W. Intermediate filaments in 3T3 cells collapse after intracellular injection of a monoclonal anti-intermediate filament antibody. Nature. 1981 May 21;291(5812):249–251. doi: 10.1038/291249a0. [DOI] [PubMed] [Google Scholar]
  35. Klymkowsky M. W., Shook D. R., Maynell L. A. Evidence that the deep keratin filament systems of the Xenopus embryo act to ensure normal gastrulation. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8736–8740. doi: 10.1073/pnas.89.18.8736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lazarides E. Intermediate filaments as mechanical integrators of cellular space. Nature. 1980 Jan 17;283(5744):249–256. doi: 10.1038/283249a0. [DOI] [PubMed] [Google Scholar]
  37. Lee M. K., Xu Z., Wong P. C., Cleveland D. W. Neurofilaments are obligate heteropolymers in vivo. J Cell Biol. 1993 Sep;122(6):1337–1350. doi: 10.1083/jcb.122.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ohara O., Gahara Y., Miyake T., Teraoka H., Kitamura T. Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. J Cell Biol. 1993 Apr;121(2):387–395. doi: 10.1083/jcb.121.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pellissier J. F., Pouget J., Charpin C., Figarella D. Myopathy associated with desmin type intermediate filaments. An immunoelectron microscopic study. J Neurol Sci. 1989 Jan;89(1):49–61. doi: 10.1016/0022-510x(89)90006-3. [DOI] [PubMed] [Google Scholar]
  40. Porte A., Stoeckel M. E., Sacrez A., Batzenschlager A. Unusual familial cardiomyopathy with storage of intermediate filaments in the cardiac muscular cells. Virchows Arch A Pathol Anat Histol. 1980;386(1):43–58. doi: 10.1007/BF00432643. [DOI] [PubMed] [Google Scholar]
  41. Quinlan R. A., Franke W. W. Heteropolymer filaments of vimentin and desmin in vascular smooth muscle tissue and cultured baby hamster kidney cells demonstrated by chemical crosslinking. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3452–3456. doi: 10.1073/pnas.79.11.3452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sakakibara S., Sekiguchi M., Konno S., Kusumoto M. Idiopathic postpartum cardiomyopathy: report of a case with special reference to its ultrastructural changes in the myocardium as studies by endomyocardial biopsy. Am Heart J. 1970 Sep;80(3):385–395. doi: 10.1016/0002-8703(70)90103-1. [DOI] [PubMed] [Google Scholar]
  43. Sarnat H. B. Myotubular myopathy: arrest of morphogenesis of myofibres associated with persistence of fetal vimentin and desmin. Four cases compared with fetal and neonatal muscle. Can J Neurol Sci. 1990 May;17(2):109–123. doi: 10.1017/s0317167100030304. [DOI] [PubMed] [Google Scholar]
  44. Sarnat H. B. Vimentin and desmin in maturing skeletal muscle and developmental myopathies. Neurology. 1992 Aug;42(8):1616–1624. doi: 10.1212/wnl.42.8.1616. [DOI] [PubMed] [Google Scholar]
  45. Sarnat H. B. Vimentin/desmin immunoreactivity of myofibres in developmental myopathies. Acta Paediatr Jpn. 1991 Apr;33(2):238–246. doi: 10.1111/j.1442-200x.1991.tb01549.x. [DOI] [PubMed] [Google Scholar]
  46. Sarria A. J., Nordeen S. K., Evans R. M. Regulated expression of vimentin cDNA in cells in the presence and absence of a preexisting vimentin filament network. J Cell Biol. 1990 Aug;111(2):553–565. doi: 10.1083/jcb.111.2.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sarria A. J., Panini S. R., Evans R. M. A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells. J Biol Chem. 1992 Sep 25;267(27):19455–19463. [PubMed] [Google Scholar]
  48. Sejersen T., Lendahl U. Transient expression of the intermediate filament nestin during skeletal muscle development. J Cell Sci. 1993 Dec;106(Pt 4):1291–1300. doi: 10.1242/jcs.106.4.1291. [DOI] [PubMed] [Google Scholar]
  49. Shafig S. A., Sande M. A., Carruthers R. R., Killip T., Milhorat A. T. Skeletal muscle in idiopathic cardiomyopathy. J Neurol Sci. 1972 Mar;15(3):303–320. doi: 10.1016/0022-510x(72)90072-x. [DOI] [PubMed] [Google Scholar]
  50. Smith W. C., Harland R. M. Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center. Cell. 1991 Nov 15;67(4):753–765. doi: 10.1016/0092-8674(91)90070-f. [DOI] [PubMed] [Google Scholar]
  51. Steinert P. M., Idler W. W., Cabral F., Gottesman M. M., Goldman R. D. In vitro assembly of homopolymer and copolymer filaments from intermediate filament subunits of muscle and fibroblastic cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3692–3696. doi: 10.1073/pnas.78.6.3692. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Takebe Y., Seiki M., Fujisawa J., Hoy P., Yokota K., Arai K., Yoshida M., Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. doi: 10.1128/mcb.8.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Telerman-Toppet N., Bauherz G., Noël S. Auriculo-ventricular block and distal myopathy with rimmed vacuoles and desmin storage. Clin Neuropathol. 1991 Mar-Apr;10(2):61–64. [PubMed] [Google Scholar]
  54. Tidball J. G. Desmin at myotendinous junctions. Exp Cell Res. 1992 Apr;199(2):206–212. doi: 10.1016/0014-4827(92)90425-8. [DOI] [PubMed] [Google Scholar]
  55. Tokuyasu K. T., Maher P. A., Singer S. J. Distributions of vimentin and desmin in developing chick myotubes in vivo. II. Immunoelectron microscopic study. J Cell Biol. 1985 Apr;100(4):1157–1166. doi: 10.1083/jcb.100.4.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Vize P. D., Melton D. A., Hemmati-Brivanlou A., Harland R. M. Assays for gene function in developing Xenopus embryos. Methods Cell Biol. 1991;36:367–387. doi: 10.1016/s0091-679x(08)60288-5. [DOI] [PubMed] [Google Scholar]
  57. Vogelstein B., Gillespie D. Preparative and analytical purification of DNA from agarose. Proc Natl Acad Sci U S A. 1979 Feb;76(2):615–619. doi: 10.1073/pnas.76.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Wong P. C., Cleveland D. W. Characterization of dominant and recessive assembly-defective mutations in mouse neurofilament NF-M. J Cell Biol. 1990 Nov;111(5 Pt 1):1987–2003. doi: 10.1083/jcb.111.5.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Xu Z., Cork L. C., Griffin J. W., Cleveland D. W. Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell. 1993 Apr 9;73(1):23–33. doi: 10.1016/0092-8674(93)90157-l. [DOI] [PubMed] [Google Scholar]
  60. van de Klundert F. A., Raats J. M., Bloemendal H. Intermediate filaments: regulation of gene expression and assembly. Eur J Biochem. 1993 Jun 1;214(2):351–366. doi: 10.1111/j.1432-1033.1993.tb17931.x. [DOI] [PubMed] [Google Scholar]

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