Diseases with Abnormal Actin and Actin-Binding Proteins in Leukocyte and Nonmuscle Cells

  • Hiroyuki Nunoi
Part of the Protein Reviews book series (PRON, volume 8)

Actin and actin-binding proteins (ABPs) in nonmuscle cells play important functional roles in defense against microbial infection, in phagocytes, and in the alignment of epithelial cells. Phagocytes migrate to sites of infection to ingest and destroy pathogens by generating reactive oxygen species and releasing the contents of their granules into phagosomes and the extracellular medium. Epithelial cells maintain their shape and use villi to remove pathogens and waste materials. The underlying mechanisms for these activities are closely associated with reorganization of the cytoskeleton. This reorganization is a cyclic process that includes polymerization of G-actin to filaments, crosslinking of filaments to form supramolecular assemblies anchored to membranes, and depolymerization of F-actin to G-actin (Moraczewska et al. 1996) (Fig. 1).


Hereditary Spherocytosis Indirect Flight Muscle Nonmuscle Myosin Nonmuscle Cell Aldrich Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambruso, D. R., Knall, C., Abell, A. N., Panepinto, J., Kurkchubasche, A., Thuman, G., Gonzales-Aller, C., Hiester, A., deBoer, M., Harbeck, R. J., Oyer, R., Johnson, G. L. and Roos, D. 2000. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proc. Natl Acad. Sci. USA 97, 4654-4659.CrossRefPubMedGoogle Scholar
  2. Boxer, L. A., Hedley-Whyte, E. T. and Stossel, T. P. 1974. Neutrophil actin dysfunction and abnormal neutrophil behavior. N. Engl. J. Med. 291, 1093-1099.PubMedCrossRefGoogle Scholar
  3. Coates, T. D., Torkildson, J. C., Torres, M., Church, J. A. and Howard, T. H. 1991. An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47 kD and 89 kD proteins. Blood 78, 1338-1346.PubMedGoogle Scholar
  4. Drummond, D. R., Hennessey, E. S. and Sparrow, J. C. 1991. Characterisation of missense mutations in the Act88F gene of Drosophila melanogaster. Mol. Genet. 226,70-80.CrossRefGoogle Scholar
  5. Fox, S. E., Lu, W., Maheshwari, A., Christensen, R. D. and Calhoun, D. A. 2005. The effects and comparative differences of neutrophil specific chemokines on neutrophil chemotaxis of the neonate. Cytokine 29, 135-140.CrossRefPubMedGoogle Scholar
  6. Gallagher, P. G. and Forget, B. G. 1998. Hematologically important mutations: spectrin and ankyrin variants in hereditary spherocytosis. Blood Cells Mol. Dis. 24, 539-543.CrossRefPubMedGoogle Scholar
  7. Gallego, M. D., de la Fuente, M. A., Anton, I. M., Snapper, S., Fuhlbrigge, R. and Geha, R. S. 2005. WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1 α. Int. Immunol. 18, 221-232.CrossRefPubMedGoogle Scholar
  8. Huttenlocher, P. R., Taravath, S. and Mojtahedi, S. 1994. Periventricular heterotopia and epilepsy. Neurology 44, 51-55.PubMedGoogle Scholar
  9. Jacobelli, J., Chmura, S. A., Buxton, D. B., Davis, M. M. and Krummel, M. F. 2004. A single class II myosin modulates T cell motility and stopping, but not synapse formation. Nat. Immunol. 5, 531-538.CrossRefPubMedGoogle Scholar
  10. Jones, G. E. 2000. Cellular signaling in macrophage migration and chemotaxis. J. Leukoc. Biol. 68, 593-602.PubMedGoogle Scholar
  11. Kaplan, J. M., Kim, S. H., North, K. N., Rennke, H., Correia, L. A., Tong, H. Q., Mathis, B. J., Rodriguez-Perez, J. C., Allen, P. G., Beggs, A. H. and Pollak, M. R. 2000. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat. Genet. 24, 251-256.CrossRefPubMedGoogle Scholar
  12. Krakow, D., Robertson, S. P., King, L. M., Morgan, T., Sebald, E. T., Bertolotto, C., Wachsmann-Hogiu, S., Acuna, D., Shapiro, S. S., Takafuta, T., Aftimos, S., Kim, C. A., Firth, H., Steiner, C. E., Cormier-Daire, V., Superti-Furga, A., Bonafe, L., Graham, J. M. Jr., Grix, A., Bacino, C. A., Allanson, J., Bialer, M. G., Lachman, R. S., Rimoin, D. L. and Cohn, D. H. 2004. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat. Genet. 36,405-410.CrossRefPubMedGoogle Scholar
  13. Kurkchubasche, A. G., Panepinto, J. A., Tracy, T. F. Jr., Thurman, G. W. and Ambruso, D. R. 2001. Clinical features of a human Rac2 mutation: A complex neutrophil dysfunction disease. J. Pediatr. 139, 141-147.CrossRefPubMedGoogle Scholar
  14. Li, Y., Guerrero, A. and Howard, T. H. 1995. The actin-binding protein, lymphocytespecific protein 1, is expressed in human leukocytes and human myeloid and lymphoid cell lines. J. Immunol. 155, 3563-3569.PubMedGoogle Scholar
  15. Maury, C. P. J., Alli, K. and Baumann, M. 1990. Finnish hereditary amyloidosis: Amino acid sequence homology between the amyloid fibril protein and human plasma gelsolin. FEBS Lett. 260, 85-87.CrossRefPubMedGoogle Scholar
  16. Moraczewska, J., Strzelecka-Golaszewska, H., Moens, P. D. J. and dos Remedios, C. G. 1996. Structural changes in the small domain of actin detected by fluorescence resonance energy transfer spectroscopy. Biochem. J. 317, 605-611.PubMedGoogle Scholar
  17. Nobes, C. D. and Hall, A. 1999. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J. Cell Biol. 144, 1235-1244.CrossRefPubMedGoogle Scholar
  18. Nunoi, H., Yamazaki, T., Tsuchiya, H., Kato, S., Malech, H. L., Matsuda, I. and Kanegasaki, S. 2000. A heterozygous mutation of β-actin associated with neutrophil dysfunction and recurrent infection. Proc. Natl Acad. Sci. USA 96, 8693-8698.CrossRefGoogle Scholar
  19. Procaccio, V., Salazar, G., Ono, S., Styers, M. L., Gearing, M., Davila, A., Jimenez, R., Juncos, J., Gutekunst, C. A., Meroni, G., Fontanella, B., Sontag, E., Sontag, J. M., Faunde, V. and Wainer, B. H. 2006. A mutation of beta-actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am. J. Hum. Genet. 78, 947-960.CrossRefPubMedGoogle Scholar
  20. Rendtorff, N. D., Zhu, M., Fagerheim, T., Antal, T. L., Jones, M., Teslovich, T. M., Gillanders, E. M., Barmada, M., Teig, E., Trent, J. M., Friderici, K. H., Stephan, D. A. and Tranebjaerg, L. 2006. A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment. Eur. J. Hum. Genet. 14, 1097-1105.CrossRefPubMedGoogle Scholar
  21. Schleicher, M., Andre, B., Andreoli, C., Eichinger, L., Haugwitz, M., Hofmann, A., Karakesisoglou, J., Stockelhuber, M. and Noegel, A. A. 1995. Structure/function studies on cytoskeletal proteins in Dictyostelium amoebae as a paradigm. FEBS Lett. 369, 38-42.CrossRefPubMedGoogle Scholar
  22. Seri, M., Cusano, R., Gangarossa, S., Caridi, G., Bordo, D., Lo Nigro, C., Ghiggeri, G. M., Ravazzolo, R., Savino, M., Del Vecchio, M., d’Apolito, M., Iolascon, A., Zelante, L. L., Savoia, A., Balduini, C. L., Noris, P., Magrini, U., Belletti, S., Heath, K. E., Babcock, M., Glucksman, M. J., Aliprandis, E., Bizzaro, N., Desnick, R. J. and Martignetti, J. A. 2000. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat. Genet. 26, 103-105.CrossRefPubMedGoogle Scholar
  23. Southwick, F. S., Dabiri, G. A. and Stossel, T. P. 1988. Neutrophil actin dysfunction is a genetic disorder associated with partial impairment of neutrophil actin assembly in three family members. J. Clin. Invest. 2, 1525-1531.CrossRefGoogle Scholar
  24. Southwick, F. S., Howard, T. H., Holbrook, T., Anderson, D. C., Stossel, T. P. and Arnaout, M. A. 1989. The relationship between CR3 deficiency and neutrophil actin assembly. Blood 73, 1973-1979.PubMedGoogle Scholar
  25. Sullivan, S. E., Staba, S. L., Gersting, J. A., Hutson, A. D., Theriaque, D., Christensen, R. D. and Calhoun, D. A. 2002. Circulating concentrations of chemokines in cord blood, neonates, and adults. Pediatr. Res. 51, 653-657.CrossRefPubMedGoogle Scholar
  26. Terashima, Y., Onai, N., Murai, M., Enomoto, M., Poonpiriya, V., Hamada, T., Motomura, K., Suwa, M., Ezaki, T., Haga, T., Kenegasaki, S. and Matsushima, K. 2005. Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis. Nat. Immunol. 6, 827-835.CrossRefPubMedGoogle Scholar
  27. van Wijk, E., Krieger, E., Kemperman, M. H., De Leenheer, E. M., Huygen, P. L., Cremers, C. W., Cremers, F. P. and Kremer, H. 2003, A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26). J. Med. Genet. 40, 879-884.CrossRefPubMedGoogle Scholar
  28. Weinberger, B., Laskin, D. L., Mariano, T. M., Sunil, V. R., DeCoste, C. J., Heck, D. E., Gardner, C. R. and Laskin, J. D. 2001. Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants. J. Leukoc. Biol. 70, 969-976.PubMedGoogle Scholar
  29. Williams, D. A., Tao, W., Yang, F., Kim, C., Gu, Y., Mansfield, P., Levine, J. E., Petryniak, B., Derrow, C. W., Harris, C., Jia, B., Zheng, Y., Ambruso, D. R., Lowe, J. B., Atkinson, S. J., Dinauer, M. C. and Boxer, L. 2000. Dominant negative mutation of the hematopoietic-specific rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood 96, 1646-1654.PubMedGoogle Scholar
  30. Witke, W., Sharpe, A. H., Hartwig, J. H., Azuma, T., Stossel, T. P. and Kwiatkowski, D. J. 1995. Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin. Cell 81, 41-51.CrossRefPubMedGoogle Scholar
  31. Wolach, B., Gavrieli, R. and Pomeranz, A. 2000. Effect of granulocyte and granulocyte macrophage colony stimulating factors (G-CSF and GM-CSF) on neonatal neutrophil functions. Pediatr. Res. 48, 369-373.CrossRefPubMedGoogle Scholar
  32. Zhu, M., Yang, T., Wei, S., DeWan, A. T., Morell, R. J., Elfenbein, J. L., Fisher, R. A., Leal, S. M., Smith, R. J. and Friderici K. H. 2003. Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26). Am. J. Hum. Genet. 73, 1082-1091.CrossRefPubMedGoogle Scholar
  33. Zicha, D., Allen, W. E., Brickell, P. M., Kinnon, C., Dunn, G. A., Jones, G. E. and Thrasher, A. J. 1998. Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome. Br. J. Haematol. 101, 659-665.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hiroyuki Nunoi
    • 1
  1. 1.Division of Pediatrics, Department of Reproductive and Developmental Medicine Faculty of MedicineUniversity of MiyazakiMiyazakiJapan

Personalised recommendations