Advertisement

DAP12 Regulates the Osteoclast Cytoskeleton

  • Wei Zou
  • Steven L. Teitelbaum
Conference paper

Abstract

The primary ITAM-containing signaling adapters, in osteoclast lineage cells, are DAP12 and the FcεRIγ chain (FcRγ). Each associates with specific immunoreceptors. DAP12 associates with the receptors TREM2 and SIRPβ1 [1], while FcRγ recognizes OSCAR [2, 3]. Both molecules also contain an ITAM motif, within their cytoplasmic domains, whose phosphorylated tyrosines provide a high-affinity binding site for Syk family kinases.

Keywords

Osteoclast Precursor Cytoskeletal Organization Actin Ring Bone Marrow Macrophage Form Actin Ring 
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.

References

  1. 1.
    Colonna M, Turnbull I, Klesney-Tait J (2007) The enigmatic function of TREM-2 in osteoclastogenesis. Adv Exp Med Biol 602:97–105PubMedCrossRefGoogle Scholar
  2. 2.
    van Beek EM, de Vries TJ, Mulder L et al (2009) Inhibitory regulation of osteoclast bone resorption by signal regulatory protein alpha. FASEB J 23:4081–4090PubMedCrossRefGoogle Scholar
  3. 3.
    Ishikawa S, Arase N, Suenaga T et al (2004) Involvement of FcRgamma in signal transduction of osteoclast-associated receptor (OSCAR). Int Immunol 16:1019–1025PubMedCrossRefGoogle Scholar
  4. 4.
    Koga T, Inui M, Inoue K et al (2004) Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428:758–763PubMedCrossRefGoogle Scholar
  5. 5.
    Mocsai A, Humphrey MB, Van Ziffle JA et al (2004) The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci USA 101:6158–6163PubMedCrossRefGoogle Scholar
  6. 6.
    Zou W, Reeve JL, Liu Y, Teitelbaum SL, Ross FP (2008) DAP12 couples c-Fms activation to the osteoclast cytoskeleton by recruitment of Syk. Mol Cell 31:422–431PubMedCrossRefGoogle Scholar
  7. 7.
    Faccio R, Zou W, Colaianni G, Teitelbaum SL, Ross FP (2003) High dose M-CSF partially rescues the Dap12−/− osteoclast phenotype. J Cell Biochem 90:871–883PubMedCrossRefGoogle Scholar
  8. 8.
    Zou W, Zhu T, Craft CS, Broekelmann TJ, Mecham RP, Teitelbaum SL (2010) Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts. J Cell Sci 123:2955–2963PubMedCrossRefGoogle Scholar
  9. 9.
    Saltel F, Chabadel A, Zhao Y et al (2006) Transmigration: a new property of mature multinucleated osteoclasts. J Bone Miner Res 21:1913–1923PubMedCrossRefGoogle Scholar
  10. 10.
    Kim N, Takami M, Rho J, Josien R, Choi Y (2002) A novel member of the leukocyte receptor complex regulates osteoclast differentiation. J Exp Med 195:201–209PubMedGoogle Scholar
  11. 11.
    Zou W, Kitaura H, Reeve J et al (2007) Syk, c-Src, the avb3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. J Cell Biol 176:877–888PubMedCrossRefGoogle Scholar
  12. 12.
    Ross FP, Teitelbaum SL (2005) avb3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol Rev 208:88–105PubMedCrossRefGoogle Scholar
  13. 13.
    Faccio R, Teitelbaum SL, Fujikawa K et al (2005) Vav3 regulates osteoclast function and bone mass. Nat Med 11:284–290PubMedCrossRefGoogle Scholar
  14. 14.
    Reeve JL, Zou W, Liu Y, Maltzman JS, Ross FP, Teitelbaum SL (2009) SLP-76 couples Syk to the osteoclast cytoskeleton. J Immunol 183:1804–1812PubMedCrossRefGoogle Scholar
  15. 15.
    Baron R (2004) Arming the osteoclast. Nat Med 10:458–460PubMedCrossRefGoogle Scholar

Copyright information

© Springer New York 2013

Authors and Affiliations

  1. 1.Department of Pathology and ImmunologyWashington University in St. Louis School of MedicineSt. LouisUSA

Personalised recommendations