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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mansfield, E. Articles by Kastner, D. L. Search for Related Content PubMed PubMed Citation Articles by Mansfield, E. Articles by Kastner, D. L. Related Collections Phagocytes Cytoskeleton Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2001, Vol. 98, No. 3, pp. 851-859 PHAGOCYTES The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments Elizabeth Mansfield, Jae Jin Chae, Hirsh D. Komarow, Tilmann M. Brotz, David M. Frucht, Ivona Aksentijevich, and Daniel L. Kastner From the Genetics Section and the Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever and intense inflammation. FMF attacks are unique in their sensitivity to the microtubule inhibitor colchicine, contrasted with their refractoriness to the anti-inflammatory effects of glucocorticoids. The FMF gene, MEFV, was recently identified by positional cloning; it is expressed at high levels in granulocytes and monocytes. The present study investigated the subcellular localization of the normal gene product, pyrin. These experiments did not support previously proposed nuclear or Golgi localizations. Instead fluorescence microscopy demonstrated colocalization of full-length GFP- and epitope-tagged pyrin with microtubules; this was markedly accentuated in paclitaxel-treated cells. Moreover, immunoblot analysis of precipitates of stabilized microtubules with recombinant pyrin demonstrated a direct interaction in vitro. Pyrin expression did not affect the stability of microtubules. Deletion constructs showed that the unique N-terminal domain of pyrin is necessary and sufficient for colocalization, whereas disease-associated mutations in the C-terminal B30.2 (rfp) domain did not disrupt this interaction. By phalloidin staining, a colocalization of pyrin with actin was also observed in perinuclear filaments and in peripheral lamellar ruffles. The proposal is made that pyrin regulates inflammatory responses at the level of leukocyte cytoskeletal organization and that the unique therapeutic effect of colchicine in FMF may be dependent on this interaction. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. L. Waite, P. Schaner, C. Hu, N. Richards, B. Balci-Peynircioglu, A. Hong, M. Fox, and D. L. Gumucio Pyrin and ASC Co-Localize to Cellular Sites that Are Rich in Polymerizing Actin Experimental Biology and Medicine, January 1, 2009; 234(1): 40 - 52. [Abstract] [Full Text] [PDF] J. J. Chae, G. Wood, K. Richard, H. Jaffe, N. T. Colburn, S. L. Masters, D. L. Gumucio, N. G. Shoham, and D. L. Kastner The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-{kappa}B through its N-terminal fragment Blood, September 1, 2008; 112(5): 1794 - 1803. [Abstract] [Full Text] [PDF] J. M. Wilmanski, T. Petnicki-Ocwieja, and K. S. Kobayashi NLR proteins: integral members of innate immunity and mediators of inflammatory diseases J. Leukoc. Biol., January 1, 2008; 83(1): 13 - 30. [Abstract] [Full Text] [PDF] S. Seshadri, M. D. Duncan, J. M. Hart, M. A. Gavrilin, and M. D. Wewers Pyrin Levels in Human Monocytes and Monocyte-Derived Macrophages Regulate IL-1beta Processing and Release J. Immunol., July 15, 2007; 179(2): 1274 - 1281. [Abstract] [Full Text] [PDF] A. Simon and J. W. M. van der Meer Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R86 - R98. [Abstract] [Full Text] [PDF] M. P. Grimaldi, G. Candore, S. Vasto, M. Caruso, G. Caimi, E. Hoffmann, G. Colonna-Romano, D. Lio, Y. Shinar, C. Franceschi, et al. Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population J. Leukoc. Biol., March 1, 2006; 79(3): 611 - 615. [Abstract] [Full Text] [PDF] R Topaloglu, F Ozaltin, E Yilmaz, S Ozen, B Balci, N Besbas, and A Bakkaloglu E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever Ann Rheum Dis, May 1, 2005; 64(5): 750 - 752. [Abstract] [Full Text] [PDF] K. Shinkai, C. Kilcline, M. K. Connolly, and I. J. Frieden The Pyrin Family of Fever Genes: Unmasking Genetic Determinants of Autoinflammatory Disease Arch Dermatol, February 1, 2005; 141(2): 242 - 247. [Full Text] [PDF] C. Kilcline, K. Shinkai, A. Bree, R. Modica, E. Von Scheven, and I. J. Frieden Neonatal-Onset Multisystem Inflammatory Disorder: The Emerging Role of Pyrin Genes in Autoinflammatory Diseases Arch Dermatol, February 1, 2005; 141(2): 248 - 253. [Abstract] [Full Text] [PDF] D. L. 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Kastner Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway PNAS, November 11, 2003; 100(23): 13501 - 13506. [Abstract] [Full Text] [PDF] C. Stehlik, L. Fiorentino, A. Dorfleutner, J.-M. Bruey, E. M. Ariza, J. Sagara, and J. C. Reed The PAAD/PYRIN-Family Protein ASC Is a Dual Regulator of a Conserved Step in Nuclear Factor {kappa}B Activation Pathways J. Exp. Med., December 16, 2002; 196(12): 1605 - 1615. [Abstract] [Full Text] [PDF] B. Balci, K. Tinaztepe, E. Yilmaz, S. Gucer, S. Ozen, R. Topaloglu, N. Besbas, M. Ozguc, and A. Bakkaloglu MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study Nephrol. Dial. Transplant., November 1, 2002; 17(11): 1921 - 1923. [Abstract] [Full Text] [PDF]

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