Gelsolin and Diseases

  • W. WITKE
Part of the Subcellular Biochemistry book series (SCBI, volume 45)


Gelsolin is a calcium-activated actin filament severing and capping protein found in many cell types and as a secreted form in the plasma of vertebrates. Mutant mice for gelsolin as well as clinical studies have shown that gelsolin is linked to a number of pathological conditions such as inflammation, cancer and amyloidosis. The tight regulation of gelsolin by calcium is crucial for its physiological role and constitutive activation leads to apoptosis. In the following we will give an overview on how gelsolin is regulated by calcium, and which clinical conditions have been linked to lack or misregulation of gelsolin


Gelsolin calcium diseases amyloidosis inflammation cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aidinis, V., P. Carninci, M. Armaka, W. Witke, V. Harokopos, N. Pavelka, D. Koczan, C. Argyropoulos, M.M. Thwin, S. Moller, K. Waki, P. Gopalakrishnakone, P. Ricciardi-Castagnoli, H.J. Thiesen, Y.Hayashizaki, and G. Kollias. 2005. Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis. PLoS Genet. 1: e48.CrossRefGoogle Scholar
  2. Allen, P.G. 2003. Actin filament uncapping localizes to ruffling lamellae and rocketing vesicles. Nat Cell Biol. 5: 972–9.PubMedCrossRefGoogle Scholar
  3. Arai, M., and D.J. Kwiatkowski. 1999. Differential developmentally regulated expression of gelsolin family members in the mouse. Dev Dyn. 215: 297–307.PubMedCrossRefGoogle Scholar
  4. Arcaro, A. 1998. The small GTP-binding protein Rac promotes the dissociation of gelsolin from actin filaments in neutrophils. J Biol Chem. 273: 805–13.PubMedCrossRefGoogle Scholar
  5. Aridor, M., and W.E. Balch. 1999. Integration of endoplasmic reticulum signaling in health and disease. Nat Med. 5: 745–51.PubMedCrossRefGoogle Scholar
  6. Arora, P.D., M. Glogauer, A. Kapus, D.J. Kwiatkowski, and C.A.McCulloch. 2004. Gelsolin mediates collagen phagocytosis through a rac-dependent step. Mol Biol Cell. 15:588–99.PubMedCrossRefGoogle Scholar
  7. Arora, P.D., P.A. Janmey,and C.A. McCulloch. 1999. A role for gelsolin in stress fiber-dependent cell contraction. Exp Cell Res. 250:155–67.PubMedCrossRefGoogle Scholar
  8. Asch, H.L., K. Head, Y. Dong, F. Natoli, J.S. Winston, J.L.Connolly, and B.B. Asch. 1996. Widespread loss of gelsolin in breast cancers of humans, mice, and rats. Cancer Res 56:4841–5.PubMedGoogle Scholar
  9. Asch, H.L., J.S. Winston, S.B. Edge, P.C. Stomper, and B.B.Asch. 1999. Down-regulation of gelsolin expression in human breast ductal carcinoma in situ with and without invasion. Breast Cancer Res Treat 55: 179–88.PubMedCrossRefGoogle Scholar
  10. Azuma, T., W. Witke, T.P.Stossel, J.H. Hartwig, and D.J. Kwiatkowski. 1998. Gelsolin is a downstream effector of rac for fibroblast motility. EmboJ 17: 1362–70.PubMedCrossRefGoogle Scholar
  11. Barkalow, K., W. Witke, D.J. Kwiatkowski, and J.H. Hartwig. 1996. Coordinated regulation of platelet actin filament barbed ends by gelsolin and capping protein. J Cell Biol 134: 389–99.PubMedCrossRefGoogle Scholar
  12. Bretscher, A., and K. Weber. 1979. Villin: the major microfilament-associated protein of the intestinal microvillus. Proc Natl Acad Sci U S A 76: 2321–5.PubMedCrossRefGoogle Scholar
  13. Bretscher, A., and K. Weber. 1980. Villin is a major protein of the microvillus cytoskeleton which binds both G and F actin in a calcium-dependent manner. Cell 20: 839–47.PubMedCrossRefGoogle Scholar
  14. Bryan, J. 1988. Gelsolin has three actin-binding sites. J Cell Biol 106: 1553–62.PubMedCrossRefGoogle Scholar
  15. Bryan, J., and S. Hwo. 1986. Definition of an N-terminal actin-binding domain and a C-terminal Ca2+regulatory domain in human brevin. J Cell Biol 102: 1439–46.PubMedCrossRefGoogle Scholar
  16. Burtnick, L.D., E.K. Koepf, J. Grimes, E.Y. Jones, D.I. Stuart, P.J. McLaughlin, and R.C. Robinson. 1997. The crystal structure of plasma gelsolin: implications for actin severing, capping, and nucleation. Cell 90: 661–70.PubMedCrossRefGoogle Scholar
  17. Burtnick, L.D., D. Urosev, E. Irobi, K. Narayan, and R.C. Robinson. 2004. Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF. Embo J 23: 2713–22.PubMedCrossRefGoogle Scholar
  18. Campbell, H.D., T. Schimansky, C. Claudianos, N. Ozsarac, A.B. Kasprzak, J.N. Cotsell, I.G. Young, H.G. de Couet, and G.L. Miklos. 1993. The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans. Proc Natl Acad Sci U S A 90: 11386–90.PubMedCrossRefGoogle Scholar
  19. Carlier, M.F. 1998. Control of actin dynamics. Curr Opin Cell Biol 10: 45–51.PubMedCrossRefGoogle Scholar
  20. Caron, E., and A. Hall. 1998. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282: 1717–21.PubMedCrossRefGoogle Scholar
  21. Carrell, R.W., and B. Gooptu. 1998. Conformational changes and disease–serpins, prions and Alzheimer’s. Curr Opin Struct Biol 8: 799–809.PubMedCrossRefGoogle Scholar
  22. Chaponnier, C., P.A. Janmey, and H.L. Yin. 1986. The actin filament-severing domain of plasma gelsolin. J Cell Biol 103: 1473–81.PubMedCrossRefGoogle Scholar
  23. Chen, C.D., M.E. Huff, J. Matteson, L. Page, R. Phillips, J.W. Kelly, and W.E. Balch. 2001. Furin initiates gelsolin familial amyloidosis in the Golgi through a defect in Ca(2+) stabilization. Embo J 20: 6277–87.PubMedCrossRefGoogle Scholar
  24. Choe, H., L.D. Burtnick, M. Mejillano, H.L. Yin, R.C. Robinson, and S. Choe. 2002. The calcium activation of gelsolin: insights from the 3A structure of the G4-G6/actin complex. J Mol Biol 324: 691–702.PubMedCrossRefGoogle Scholar
  25. Cunningham, C.C., T.P. Stossel, and D.J. Kwiatkowski. 1991. Enhanced motility in NIH 3T3 fibroblasts that overexpress gelsolin. Science 251: 1233–6.PubMedCrossRefGoogle Scholar
  26. Dabiri, G.A., C.L. Young, J. Rosenbloom, and F.S. Southwick. 1992. Molecular cloning of human macrophage capping protein cDNA. A unique member of the gelsolin/villin family expressed primarily in macrophages. J Biol Chem 267: 16545–52.PubMedGoogle Scholar
  27. Dahl, B., F.V. Schiodt, P. Ott, R. Gvozdenovic, H.L. Yin, and W.M. Lee. 1999. Plasma gelsolin is reduced in trauma patients. Shock 12: 102–4.PubMedCrossRefGoogle Scholar
  28. Davoodian, K., B.W. Ritchings, R. Ramphal, and M.R. Bubb. 1997. Gelsolin activates DNase I in vitro and cystic fibrosis sputum. Biochemistry 36: 9637–41.PubMedCrossRefGoogle Scholar
  29. De Corte, V., E. Bruyneel, C. Boucherie, M. Mareel, J. Vandekerckhove, and J. Gettemans. 2002. Gelsolin-induced epithelial cell invasion is dependent on Ras-Rac signaling. Embo J 21: 6781–90.PubMedCrossRefGoogle Scholar
  30. Dosaka-Akita, H., F. Hommura, H. Fujita, I. Kinoshita, M. Nishi, T. Morikawa, H. Katoh, Y. Kawakami, and N. Kuzumaki. 1998. Frequent loss of gelsolin expression in non-small cell lung cancers of heavy smokers. Cancer Res 58: 322–7.PubMedGoogle Scholar
  31. Ehrlich, H.P., G.M. Allison, M.J. Page, W.A. Kolton, and M. Graham. 2000. Increased gelsolin expression and retarded collagen lattice contraction with smooth muscle cells from Crohn’s diseased intestine. J Cell Physiol 182: 303–9.PubMedCrossRefGoogle Scholar
  32. Fishkind, D.J., and Y.L. Wang. 1995. New horizons for cytokinesis. Curr Opin Cell Biol 7: 23–31.PubMedCrossRefGoogle Scholar
  33. Fujita, H., F. Okada, J. Hamada, M. Hosokawa, T. Moriuchi, R.C. Koya, and N. Kuzumaki. 2001. Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect. Int J Cancer 93: 773–80.PubMedCrossRefGoogle Scholar
  34. Furukawa, K., W. Fu, Y. Li, W. Witke, D.J. Kwiatkowski, and M.P. Mattson. 1997. The actin-severing protein gelsolin modulates calcium channel and NMDA receptor activities and vulnerability to excitotoxicity in hippocampal neurons. J Neurosci 17: 8178–86.PubMedGoogle Scholar
  35. Goshima, M., K. Kariya, Y. Yamawaki-Kataoka, T. Okada, M. Shibatohge, F. Shima, E. Fujimoto, and T. Kataoka. 1999. Characterization of a novel Ras-binding protein Ce-FLI-1 comprising leucine-rich repeats and gelsolin-like domains. Biochem Biophys Res Commun 257: 111–6.PubMedCrossRefGoogle Scholar
  36. Hatanaka, H., K. Ogura, K. Moriyama, S. Ichikawa, I. Yahara, and F. Inagaki. 1996. Tertiary structure of destrin and structural similarity between two actin-regulating protein families. Cell 85: 1047–55.PubMedCrossRefGoogle Scholar
  37. Huff, M.E., L.J. Page, W.E. Balch, and J.W. Kelly. 2003. Gelsolin domain 2 Ca2+affinity determines susceptibility to furin proteolysis and familial amyloidosis of finnish type. J Mol Biol 334: 119–27.PubMedCrossRefGoogle Scholar
  38. Isaacson, R.L., A.G. Weeds, and A.R. Fersht. 1999. Equilibria and kinetics of folding of gelsolin domain 2 and mutants involved in familial amyloidosis-Finnish type. Proc Natl Acad Sci U S A 96: 11247–52.PubMedCrossRefGoogle Scholar
  39. Ismailov, II, B.K. Berdiev, V.G. Shlyonsky, C.M. Fuller, A.G. Prat, B. Jovov, H.F. Cantiello, D.A. Ausiello, and D.J. Benos. 1997. Role of actin in regulation of epithelial sodium channels by CFTR. Am J Physiol 272: C1077–86.PubMedGoogle Scholar
  40. Janmey, P.A., K. Iida, H.L. Yin, and T.P. Stossel. 1987. Polyphosphoinositide micelles and polyphosphoinositide-containing vesicles dissociate endogenous gelsolin-actin complexes and promote actin assembly from the fast-growing end of actin filaments blocked by gelsolin. J Biol Chem 262: 12228–36.PubMedGoogle Scholar
  41. Janmey, P.A., T.P. Stossel, and S.E. Lind. 1986. Sequential binding of actin monomers to plasma gelsolin and its inhibition by vitamin D-binding protein. Biochem Biophys Res Commun 136: 72–9.PubMedCrossRefGoogle Scholar
  42. Kamada, S., H. Kusano, H. Fujita, M. Ohtsu, R.C. Koya, N. Kuzumaki, and Y. Tsujimoto. 1998. A cloning method for caspase substrates that uses the yeast two-hybrid system: cloning of the antiapoptotic gene gelsolin. Proc Natl Acad Sci U S A 95: 8532–7.PubMedCrossRefGoogle Scholar
  43. Kangas, H., I. Ulmanen, T. Paunio, D.J. Kwiatkowski, M. Lehtovirta, A. Jalanko, and L. Peltonen. 1999. Functional consequences of amyloidosis mutation for gelsolin polypeptide – analysis of gelsolin-actin interaction and gelsolin processing in gelsolin knock-out fibroblasts. FEBS Lett 454: 233–9.PubMedCrossRefGoogle Scholar
  44. Kelly, J.W. 1996. Alternative conformations of amyloidogenic proteins govern their behavior. Curr Opin Struct Biol 6: 11–7.PubMedCrossRefGoogle Scholar
  45. Kothakota, S., T. Azuma, C. Reinhard, A. Klippel, J. Tang, K. Chu, T.J. McGarry, M.W. Kirschner, K. Koths, D.J. Kwiatkowski, and L.T. Williams. 1997. Caspase-3-generated fragment of gelsolin:effector of morphological change in apoptosis. Science 278: 294–8.PubMedCrossRefGoogle Scholar
  46. Kuzumaki, N., M. Tanaka, N. Sakai, and H. Fujita. 1997. [Tumor suppressive function of gelsolin]. Gan To Kagaku Ryoho 24: 1436–41.PubMedGoogle Scholar
  47. Kwiatkowski, D.J. 1999. Functions of gelsolin: motility, signaling, apoptosis, cancer. Curr Opin Cell Biol 11: 103–8.PubMedCrossRefGoogle Scholar
  48. Kwiatkowski, D.J., P.A. Janmey, J.E. Mole, and H.L. Yin. 1985. Isolation and properties of two actin-binding domains in gelsolin. J Biol Chem 260: 15232–8.PubMedGoogle Scholar
  49. Kwiatkowski, D.J., P.A. Janmey, and H.L. Yin. 1989. Identification of critical functional and regulatory domains in gelsolin. J Cell Biol 108: 1717–26.PubMedCrossRefGoogle Scholar
  50. Kwiatkowski, D.J., R. Mehl, S. Izumo, B. Nadal-Ginard, and H.L. Yin. 1988. Muscle is the major source of plasma gelsolin. J Biol Chem 263: 8239–43.PubMedGoogle Scholar
  51. Kwiatkowski, D.J., T.P. Stossel, S.H. Orkin, J.E. Mole, H.R. Colten, and H.L. Yin. 1986. Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain. Nature 323: 455–8.PubMedCrossRefGoogle Scholar
  52. Lu, M., W. Witke, D.J. Kwiatkowski, and K.S. Kosik. 1997. Delayed retraction of filopodia in gelsolin null mice. J Cell Biol 138: 1279–87.PubMedCrossRefGoogle Scholar
  53. Lueck, A., D. Brown, and D.J. Kwiatkowski. 1998. The actin-binding proteins adseverin and gelsolin are both highly expressed but differentially localized in kidney and intestine. J Cell Sci 111 ( Pt24): 3633–43.PubMedGoogle Scholar
  54. Maekawa, S., and H. Sakai. 1990. Inhibition of actin regulatory activity of the 74-kDa protein from bovine adrenal medulla (adseverin) by some phospholipids. J Biol Chem 265: 10940–2.PubMedGoogle Scholar
  55. Maury, C.P. 1991. Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin. J Clin Invest 87: 1195–9.PubMedCrossRefGoogle Scholar
  56. Maury, C.P., M. Liljestrom, G. Boysen, T. Tornroth, A. de la Chapelle, and E.L. Nurmiaho-Lassila. 2000. Danish type gelsolin related amyloidosis:654G-T mutation is associated with a disease pathogenetically and clinically similar to that caused by the 654G-A mutation (familial amyloidosis of the Finnish type). J Clin Pathol 53: 95–9.PubMedCrossRefGoogle Scholar
  57. Maury, C.P., M. Liljestrom, S. Tiitinen, K. Laiho, K. Kaarela, and C. Ehnholm. 2001. Apolipoprotein E phenotypes in rheumatoid arthritis with or without amyloidosis. Amyloid 8: 270–3.PubMedGoogle Scholar
  58. Mayadas, T.N., R.C. Johnson, H. Rayburn, R.O. Hynes, and D.D. Wagner. 1993. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 74: 541–54.PubMedCrossRefGoogle Scholar
  59. McGough, A., W. Chiu, and M. Way. 1998. Determination of the gelsolin binding site on F-actin:implications for severing and capping. Biophys J 74: 764–72.PubMedGoogle Scholar
  60. McGough, A.M., C.J. Staiger, J.K. Min, and K.D. Simonetti. 2003. The gelsolin family of actin regulatory proteins: modular structures, versatile functions. FEBS Lett 552: 75–81.PubMedCrossRefGoogle Scholar
  61. McLaughlin, P.J., J.T. Gooch, H.G. Mannherz, and A.G. Weeds. 1993. Structure of gelsolin segment 1-actin complex and the mechanism of filament severing. Nature 364: 685–92.PubMedCrossRefGoogle Scholar
  62. Mielnicki, L.M., A.M. Ying, K.L. Head, H.L. Asch, and B.B. Asch. 1999. Epigenetic regulation of gelsolin expression in human breast cancer cells. Exp Cell Res 249: 161–76.PubMedCrossRefGoogle Scholar
  63. Mullauer, L., H. Fujita, A. Ishizaki, and N. Kuzumaki. 1993. Tumor-suppressive function of mutated gelsolin in ras-transformed cells. Oncogene 8: 2531–6.PubMedGoogle Scholar
  64. Onda, H., A. Lueck, P.W. Marks, H.B. Warren, and D.J.Kwiatkowski. 1999. Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest 104: 687–95.PubMedGoogle Scholar
  65. Page, L.J., M.E. Huff, J.W. Kelly, and W.E. Balch. 2004. Ca2+binding protects against gelsolin amyloidosis. Biochem Biophys Res Commun 322: 1105–10.PubMedCrossRefGoogle Scholar
  66. Paunio, T., H. Kangas, O. Heinonen, M.H. Buc-Caron, J.J. Robert, S. Kaasinen, I. Julkunen, J. Mallet, and L. Peltonen. 1998. Cells of the neuronal lineage play a major role in the generation of amyloid precursor fragments in gelsolin-related amyloidosis. J Biol Chem 273: 16319–24.PubMedCrossRefGoogle Scholar
  67. Pollard, T.D., and J.A. Cooper. 1986. Actin and actin-binding proteins. A critical evaluation of mechanisms and functions. Annu Rev Biochem 55: 987–1035.PubMedCrossRefGoogle Scholar
  68. Pope, B., S. Maciver, and A. Weeds. 1995. Localization of the calcium-sensitive actin monomer binding site in gelsolin to segment 4 and identification of calcium binding sites. Biochemistry 34: 1583–8.PubMedCrossRefGoogle Scholar
  69. Pope, B., M. Way, and A.G. Weeds. 1991. Two of the three actin-binding domains of gelsolin bind to the same subdomain of actin. Implications of capping and severing mechanisms. FEBS Lett 280: 70–4.PubMedCrossRefGoogle Scholar
  70. Prasad, S.C., P.J. Thraves, A. Dritschilo, and M.R. Kuettel. 1997. Protein expression changes associated with radiation-induced neoplastic progression of human prostate epithelial cells. Electrophoresis 18: 629–37.PubMedCrossRefGoogle Scholar
  71. Prendergast, G.C., and E.B. Ziff. 1991. Mbh 1: a novel gelsolin/severin-related protein which binds actin in vitro and exhibits nuclear localization in vivo. Embo J 10: 757–66.PubMedGoogle Scholar
  72. Rodriguez Del Castillo, A., S. Lemaire, L. Tchakarov, M. Jeyapragasan, J.P. Doucet, M.L. Vitale, and J.M. Trifaro. 1990. Chromaffin cell scinderin, a novel calcium-dependent actin filament-severing protein. Embo J 9: 43–52.Google Scholar
  73. Rothenbach, P.A., B. Dahl, J.J. Schwartz, G.E. O’Keefe, M. Yamamoto, W.M. Lee, J.W. Horton, H.L. Yin, and R.H. Turnage. 2004. Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction. J Appl Physiol 96: 25–31.PubMedCrossRefGoogle Scholar
  74. Sagawa, N., H. Fujita, Y. Banno, Y. Nozawa, H. Katoh, and N. Kuzumaki. 2003. Gelsolin suppresses tumorigenicity through inhibiting PKC activation in a human lung cancer cell line, PC10. Br J Cancer 88: 606–12.PubMedCrossRefGoogle Scholar
  75. Selden, L.A., H.J. Kinosian, J. Newman, B. Lincoln, C. Hurwitz, L.C. Gershman, and J.E. Estes. 1998. Severing of F-actin by the amino-terminal half of gelsolin suggests internal cooperativity in gelsolin. Biophys J 75: 3092–100.PubMedCrossRefGoogle Scholar
  76. Serrander, L., P. Skarman, B. Rasmussen, W. Witke, D.P. Lew, K.H. Krause, O. Stendahl, and O. Nusse. 2000. Selective inhibition of IgG-mediated phagocytosis in gelsolin-deficient murine neutrophils. JImmunol 165: 2451–7.Google Scholar
  77. Sheils, C.A., J. Kas, W. Travassos, P.G. Allen, P.A. Janmey, M.E. Wohl, and T.P. Stossel. 1996. Actin filaments mediate DNA fiber formation in chronic inflammatory airway disease. Am J Pathol 148: 919–27.PubMedGoogle Scholar
  78. Shieh, D.B., J. Godleski, J.E. Herndon, 2nd, T. Azuma, H. Mercer, D.J. Sugarbaker, and D.J. Kwiatkowski. 1999. Cell motility as a prognostic factor in Stage I nonsmall cell lung carcinoma: the role of gelsolin expression. Cancer 85: 47–57.PubMedCrossRefGoogle Scholar
  79. Southwick, F.S., and M.J. DiNubile. 1986. Rabbit alveolarmacrophages contain a Ca2+-sensitive, 41,000-dalton protein which reversibly blocks the “barbed” ends of actin filaments but does not sever them. J Biol Chem 261: 14191–5.PubMedGoogle Scholar
  80. Suhler, E., W. Lin, H.L. Yin, and W.M. Lee. 1997. Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis. Crit Care Med 25: 594–8.PubMedCrossRefGoogle Scholar
  81. Sun, H.Q., M. Yamamoto, M. Mejillano, and H.L. Yin. 1999. Gelsolin, a multifunctional actin regulatory protein. J Biol Chem 274: 33179–82.PubMedCrossRefGoogle Scholar
  82. Tanaka, J., and K. Sobue. 1994. Localization and characterization of gelsolin in nervous tissues: gelsolin is specifically enriched in myelin-forming cells. J Neurosci 14: 1038–52.PubMedGoogle Scholar
  83. Tanaka, M., L. Mullauer, Y. Ogiso, H. Fujita, S. Moriya, K. Furuuchi, T. Harabayashi, N. Shinohara, T. Koyanagi, and N. Kuzumaki. 1995. Gelsolin: a candidate for suppressor of human bladder cancer. Cancer Res 55: 3228–32.PubMedGoogle Scholar
  84. Teubner, A., I. Sobek-Klocke, H. Hinssen, and U. Eichenlaub-Ritter. 1994. Distribution of gelsolin in mouse ovary. Cell Tissue Res 276: 535–44.PubMedGoogle Scholar
  85. Thor, A.D., S.M. Edgerton, S. Liu, D.H. Moore, 2nd, and D.J. Kwiatkowski. 2001. Gelsolin as a negative prognostic factor and effector of motility in erbB-2-positive epidermal growth factor receptor-positive breast cancers. Clin Cancer Res 7: 2415–24.PubMedGoogle Scholar
  86. Vasconcellos, C.A., P.G. Allen, M.E. Wohl, J.M. Drazen, P.A. Janmey, and T.P. Stossel. 1994. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science 263: 969–71.PubMedCrossRefGoogle Scholar
  87. Vouyiouklis, D.A., and P.J. Brophy. 1997. A novel gelsolin isoform expressed by oligodendrocytes in the central nervous system. J Neurochem 69: 995–1005.PubMedCrossRefGoogle Scholar
  88. Wagner, E.F., and R. Eferl. 2005. Fos/AP-1 proteins in bone and the immune system. Immunol Rev 208: 126–40.PubMedCrossRefGoogle Scholar
  89. Way, M., and P. Matsudaira. 1993. The secrets of severing? Curr Biol 3: 887–90.PubMedCrossRefGoogle Scholar
  90. Way, M., B. Pope, J. Gooch, M. Hawkins, and A.G. Weeds. 1990. Identification of a region in segment 1 of gelsolin critical for actin binding. Embo J 9: 4103–9.PubMedGoogle Scholar
  91. Way, M., B. Pope, and A. Weeds. 1991. Molecular biology of actin binding proteins:evidence for a common structural domain in the F-actin binding sites of gelsolin and alpha-actinin. J Cell Sci Suppl 14: 91–4.PubMedGoogle Scholar
  92. Way, M., B. Pope, and A.G. Weeds. 1992. Are the conserved sequences in segment 1 of gelsolin important for binding actin? J Cell Biol 116: 1135–43.PubMedCrossRefGoogle Scholar
  93. Weeds, A.G., J. Gooch, P. McLaughlin, and C.P. Maury. 1993. Variant plasma gelsolin responsible for familial amyloidosis (Finnish type) has defective actin severing activity. FEBS Lett 335: 119–23.PubMedCrossRefGoogle Scholar
  94. Weeds, A.G., J. Gooch, P. McLaughlin, B. Pope, M. Bengtsdotter, and R. Karlsson. 1995. Identification of the trapped calcium in the gelsolin segment 1-actin complex: implications for the role of calcium in the control of gelsolin activity. FEBS Lett 360: 227–30.PubMedCrossRefGoogle Scholar
  95. Wegner, A. 1976. Head to tail polymerization of actin. J Mol Biol 108: 139–50.PubMedCrossRefGoogle Scholar
  96. Welch, M.D., A. Mallavarapu, J. Rosenblatt, and T.J. Mitchison. 1997. Actin dynamics in vivo. Curr Opin Cell Biol 9: 54–61.PubMedCrossRefGoogle Scholar
  97. Witke, W., W. Li, D.J. Kwiatkowski, and F.S. Southwick. 2001. Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing. J Cell Biol 154: 775–84.PubMedCrossRefGoogle Scholar
  98. Witke, W., A.H. Sharpe, J.H. Hartwig, T. Azuma, T.P. Stossel, and P. Chang. 1995. Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin. Cell 81: 41–51.PubMedCrossRefGoogle Scholar
  99. Yamada, K.M., and B. Geiger. 1997. Molecular interactions in cell adhesion complexes. Curr Opin Cell Biol 9: 76–85.PubMedCrossRefGoogle Scholar
  100. Yin, H.L., D.J. Kwiatkowski, J.E. Mole, and F.S. Cole. 1984. Structure and biosynthesis of cytoplasmic and secreted variants of gelsolin. J Biol Chem 259: 5271–6.PubMedGoogle Scholar
  101. Yin, H.L., and T.P. Stossel. 1979. Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature 281: 583–6.PubMedCrossRefGoogle Scholar
  102. Yin, H.L., and J.T. Stull. 1999. Proteins that regulate dynamic actin remodeling in response to membrane signaling minireview series. J Biol Chem 274: 32529–30.PubMedCrossRefGoogle Scholar
  103. Yin, H.L., K.S. Zaner, and T.P. Stossel. 1980. Ca2+control of actin gelation. Interaction of gelsolin with actin filaments and regulation of actin gelation. J Biol Chem 255: 9494–500.PubMedGoogle Scholar
  104. Yu, F.X., P.A. Johnston, T.C. Sudhof, and H.L. Yin. 1990. gCap39, a calcium ion- and polyphosphoinositide-regulated actin capping protein. Science 250: 1413–5.PubMedCrossRefGoogle Scholar
  105. Zerovnik, E. 2002. Amyloid-fibril formation. Proposed mechanisms and relevance to conformational disease. Eur J Biochem 269: 3362–71.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

    • 1
  • W. WITKE
    • 2
  1. 1.Direzione ScientificaIRCCS Fondazione Ospedale Policlinico, Mangiagalli e Regina ElenaViaFrancesco Sforza 28Italy
  2. 2.EMBL MonterotondoVia Ramarini 32, 00015 MonterotondoItaly

Personalised recommendations