Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Sep 1;111(3):1069–1079. doi: 10.1083/jcb.111.3.1069

Fimbrin is a homologue of the cytoplasmic phosphoprotein plastin and has domains homologous with calmodulin and actin gelation proteins

PMCID: PMC2116281  PMID: 2391360

Abstract

Fimbrin is an actin-bundling protein found in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia. The complete protein sequence (630 residues) of chicken intestine fimbrin has been determined from two full-length cDNA clones. The sequence encodes a small amino-terminal domain (115 residues) that is homologous with two calcium-binding sites of calmodulin and a large carboxy-terminal domain (500 residues) consisting of a fourfold-repeated 125-residue sequence. This repeat is homologous with the actin-binding domain of alpha- actinin and the amino-terminal domains of dystrophin, actin-gelation protein, and beta-spectrin. The presence of this duplicated domain in fimbrin links actin bundling proteins and gelation proteins into a common family of actin cross-linking proteins. Fimbrin is also homologous in sequence with human L-plastin and T-plastin. L-plastin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to IL 1 or phorbol myristate acetate. T- plastin is found in cells of solid tissues where it does not become phosphorylated. Neoplastic cells derived from solid tissues express both isoforms. The differences in expression, sequence, and phosphorylation suggest possible functional differences between fimbrin isoforms.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson N. L., Gemmell M. A., Coussens P. M., Murao S., Huberman E. Specific protein phosphorylation in human promyelocytic HL-60 leukemia cells susceptible or resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate. Cancer Res. 1985 Oct;45(10):4955–4962. [PubMed] [Google Scholar]
  2. Baron M. D., Davison M. D., Jones P., Critchley D. R. The sequence of chick alpha-actinin reveals homologies to spectrin and calmodulin. J Biol Chem. 1987 Dec 25;262(36):17623–17629. [PubMed] [Google Scholar]
  3. Bazari W. L., Matsudaira P., Wallek M., Smeal T., Jakes R., Ahmed Y. Villin sequence and peptide map identify six homologous domains. Proc Natl Acad Sci U S A. 1988 Jul;85(14):4986–4990. doi: 10.1073/pnas.85.14.4986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blanchard A., Ohanian V., Critchley D. The structure and function of alpha-actinin. J Muscle Res Cell Motil. 1989 Aug;10(4):280–289. doi: 10.1007/BF01758424. [DOI] [PubMed] [Google Scholar]
  5. Bretscher A. Fimbrin is a cytoskeletal protein that crosslinks F-actin in vitro. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6849–6853. doi: 10.1073/pnas.78.11.6849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bretscher A., Weber K. Fimbrin, a new microfilament-associated protein present in microvilli and other cell surface structures. J Cell Biol. 1980 Jul;86(1):335–340. doi: 10.1083/jcb.86.1.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bretscher A., Weber K. Villin is a major protein of the microvillus cytoskeleton which binds both G and F actin in a calcium-dependent manner. Cell. 1980 Jul;20(3):839–847. doi: 10.1016/0092-8674(80)90330-x. [DOI] [PubMed] [Google Scholar]
  8. Brotschi E. A., Hartwig J. H., Stossel T. P. The gelation of actin by actin-binding protein. J Biol Chem. 1978 Dec 25;253(24):8988–8993. [PubMed] [Google Scholar]
  9. Bryan J., Kane R. E. Separation and interaction of the major components of sea urchin actin gel. J Mol Biol. 1978 Oct 25;125(2):207–224. doi: 10.1016/0022-2836(78)90345-5. [DOI] [PubMed] [Google Scholar]
  10. Byers T. J., Husain-Chishti A., Dubreuil R. R., Branton D., Goldstein L. S. Sequence similarity of the amino-terminal domain of Drosophila beta spectrin to alpha actinin and dystrophin. J Cell Biol. 1989 Oct;109(4 Pt 1):1633–1641. doi: 10.1083/jcb.109.4.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bähler M., Greengard P. Synapsin I bundles F-actin in a phosphorylation-dependent manner. Nature. 1987 Apr 16;326(6114):704–707. doi: 10.1038/326704a0. [DOI] [PubMed] [Google Scholar]
  12. Carley W. W., Bretscher A., Webb W. W. F-actin aggregates in transformed cells contain alpha-actinin and fimbrin but apparently lack tropomyosin. Eur J Cell Biol. 1986 Jan;39(2):313–320. [PubMed] [Google Scholar]
  13. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  14. Condeelis J., Vahey M., Carboni J. M., DeMey J., Ogihara S. Properties of the 120,000- and 95,000-dalton actin-binding proteins from Dictyostelium discoideum and their possible functions in assembling the cytoplasmic matrix. J Cell Biol. 1984 Jul;99(1 Pt 2):119s–126s. doi: 10.1083/jcb.99.1.119s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davison M. D., Critchley D. R. alpha-Actinins and the DMD protein contain spectrin-like repeats. Cell. 1988 Jan 29;52(2):159–160. doi: 10.1016/0092-8674(88)90503-x. [DOI] [PubMed] [Google Scholar]
  16. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Glenney J. R., Jr, Geisler N., Kaulfus P., Weber K. Demonstration of at least two different actin-binding sites in villin, a calcium-regulated modulator of F-actin organization. J Biol Chem. 1981 Aug 10;256(15):8156–8161. [PubMed] [Google Scholar]
  18. Glenney J. R., Jr, Kaulfus P., Matsudaira P., Weber K. F-actin binding and bundling properties of fimbrin, a major cytoskeletal protein of microvillus core filaments. J Biol Chem. 1981 Sep 10;256(17):9283–9288. [PubMed] [Google Scholar]
  19. Goldstein D., Djeu J., Latter G., Burbeck S., Leavitt J. Abundant synthesis of the transformation-induced protein of neoplastic human fibroblasts, plastin, in normal lymphocytes. Cancer Res. 1985 Nov;45(11 Pt 2):5643–5647. [PubMed] [Google Scholar]
  20. Hammonds R. G., Jr Protein sequence of DMD gene is related to actin-binding domain of alpha-actinin. Cell. 1987 Oct 9;51(1):1–1. doi: 10.1016/0092-8674(87)90002-x. [DOI] [PubMed] [Google Scholar]
  21. Hartwig J. H., Stossel T. P. Isolation and properties of actin, myosin, and a new actinbinding protein in rabbit alveolar macrophages. J Biol Chem. 1975 Jul 25;250(14):5696–5705. [PubMed] [Google Scholar]
  22. Hesterberg L. K., Weber K. Demonstration of three distinct calcium-binding sites in villin, a modulator of actin assembly. J Biol Chem. 1983 Jan 10;258(1):365–369. [PubMed] [Google Scholar]
  23. Husain-Chishti A., Levin A., Branton D. Abolition of actin-bundling by phosphorylation of human erythrocyte protein 4.9. Nature. 1988 Aug 25;334(6184):718–721. doi: 10.1038/334718a0. [DOI] [PubMed] [Google Scholar]
  24. Imamura M., Endo T., Kuroda M., Tanaka T., Masaki T. Substructure and higher structure of chicken smooth muscle alpha-actinin molecule. J Biol Chem. 1988 Jun 5;263(16):7800–7805. [PubMed] [Google Scholar]
  25. Jaken S., Leach K., Klauck T. Association of type 3 protein kinase C with focal contacts in rat embryo fibroblasts. J Cell Biol. 1989 Aug;109(2):697–704. doi: 10.1083/jcb.109.2.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Koenig M., Monaco A. P., Kunkel L. M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 1988 Apr 22;53(2):219–228. doi: 10.1016/0092-8674(88)90383-2. [DOI] [PubMed] [Google Scholar]
  27. Lemaire C., Heilig R., Mandel J. L. The chicken dystrophin cDNA: striking conservation of the C-terminal coding and 3' untranslated regions between man and chicken. EMBO J. 1988 Dec 20;7(13):4157–4162. doi: 10.1002/j.1460-2075.1988.tb03311.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lin C. S., Aebersold R. H., Kent S. B., Varma M., Leavitt J. Molecular cloning and characterization of plastin, a human leukocyte protein expressed in transformed human fibroblasts. Mol Cell Biol. 1988 Nov;8(11):4659–4668. doi: 10.1128/mcb.8.11.4659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lin C. S., Aebersold R. H., Leavitt J. Correction of the N-terminal sequences of the human plastin isoforms by using anchored polymerase chain reaction: identification of a potential calcium-binding domain. Mol Cell Biol. 1990 Apr;10(4):1818–1821. doi: 10.1128/mcb.10.4.1818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Louvard D. The function of the major cytoskeletal components of the brush border. Curr Opin Cell Biol. 1989 Feb;1(1):51–57. doi: 10.1016/s0955-0674(89)80036-5. [DOI] [PubMed] [Google Scholar]
  31. Matsudaira P. T., Burgess D. R. Identification and organization of the components in the isolated microvillus cytoskeleton. J Cell Biol. 1979 Dec;83(3):667–673. doi: 10.1083/jcb.83.3.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Matsudaira P., Jakes R., Cameron L., Atherton E. Mapping the cysteine residues and actin-binding regions of villin by using antisera to the amino and carboxyl termini of the molecule. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6788–6792. doi: 10.1073/pnas.82.20.6788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Matsudaira P., Janmey P. Pieces in the actin-severing protein puzzle. Cell. 1988 Jul 15;54(2):139–140. doi: 10.1016/0092-8674(88)90542-9. [DOI] [PubMed] [Google Scholar]
  34. Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed] [Google Scholar]
  35. Matsushima K., Shiroo M., Kung H. F., Copeland T. D. Purification and characterization of a cytosolic 65-kilodalton phosphoprotein in human leukocytes whose phosphorylation is augmented by stimulation with interleukin 1. Biochemistry. 1988 May 17;27(10):3765–3770. doi: 10.1021/bi00410a037. [DOI] [PubMed] [Google Scholar]
  36. Mimura N., Asano A. Isolation and characterization of a conserved actin-binding domain from rat hepatic actinogelin, rat skeletal muscle, and chicken gizzard alpha-actinins. J Biol Chem. 1986 Aug 15;261(23):10680–10687. [PubMed] [Google Scholar]
  37. Morrow J. S. The spectrin membrane skeleton: emerging concepts. Curr Opin Cell Biol. 1989 Feb;1(1):23–29. doi: 10.1016/s0955-0674(89)80032-8. [DOI] [PubMed] [Google Scholar]
  38. Noegel A. A., Rapp S., Lottspeich F., Schleicher M., Stewart M. The Dictyostelium gelation factor shares a putative actin binding site with alpha-actinins and dystrophin and also has a rod domain containing six 100-residue motifs that appear to have a cross-beta conformation. J Cell Biol. 1989 Aug;109(2):607–618. doi: 10.1083/jcb.109.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Noegel A., Witke W., Schleicher M. Calcium-sensitive non-muscle alpha-actinin contains EF-hand structures and highly conserved regions. FEBS Lett. 1987 Sep 14;221(2):391–396. doi: 10.1016/0014-5793(87)80962-6. [DOI] [PubMed] [Google Scholar]
  40. Pollard T. D., Cooper J. A. Actin and actin-binding proteins. A critical evaluation of mechanisms and functions. Annu Rev Biochem. 1986;55:987–1035. doi: 10.1146/annurev.bi.55.070186.005011. [DOI] [PubMed] [Google Scholar]
  41. Putkey J. A., Slaughter G. R., Means A. R. Bacterial expression and characterization of proteins derived from the chicken calmodulin cDNA and a calmodulin processed gene. J Biol Chem. 1985 Apr 25;260(8):4704–4712. [PubMed] [Google Scholar]
  42. Salisbury J. L., Condeelis J. S., Maihle N. J., Satir P. Calmodulin localization during capping and receptor-mediated endocytosis. Nature. 1981 Nov 12;294(5837):163–166. doi: 10.1038/294163a0. [DOI] [PubMed] [Google Scholar]
  43. Siegel D. L., Branton D. Partial purification and characterization of an actin-bundling protein, band 4.9, from human erythrocytes. J Cell Biol. 1985 Mar;100(3):775–785. doi: 10.1083/jcb.100.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Simmen R. C., Tanaka T., Ts'ui K. F., Putkey J. A., Scott M. J., Lai E. C., Means A. R. The structural organization of the chicken calmodulin gene. J Biol Chem. 1985 Jan 25;260(2):907–912. [PubMed] [Google Scholar]
  45. Stein J. P., Munjaal R. P., Lagace L., Lai E. C., O'Malley B. W., Means A. R. Tissue-specific expression of a chicken calmodulin pseudogene lacking intervening sequences. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6485–6489. doi: 10.1073/pnas.80.21.6485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Strynadka N. C., James M. N. Crystal structures of the helix-loop-helix calcium-binding proteins. Annu Rev Biochem. 1989;58:951–998. doi: 10.1146/annurev.bi.58.070189.004511. [DOI] [PubMed] [Google Scholar]
  47. Studier F. W., Moffatt B. A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol. 1986 May 5;189(1):113–130. doi: 10.1016/0022-2836(86)90385-2. [DOI] [PubMed] [Google Scholar]
  48. Sutoh K., Mabuchi I. Improved method for mapping the binding site of an actin-binding protein in the actin sequence. Use of a site-directed antibody against the N-terminal region of actin as a probe of its N-terminus. Biochemistry. 1986 Oct 7;25(20):6186–6192. doi: 10.1021/bi00368a053. [DOI] [PubMed] [Google Scholar]
  49. Wang K., Ash J. F., Singer S. J. Filamin, a new high-molecular-weight protein found in smooth muscle and non-muscle cells. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4483–4486. doi: 10.1073/pnas.72.11.4483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yamashiro-Matsumura S., Matsumura F. Purification and characterization of an F-actin-bundling 55-kilodalton protein from HeLa cells. J Biol Chem. 1985 Apr 25;260(8):5087–5097. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES