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Syntenin Is Expressed in Human Follicular Dendritic Cells and Involved in the Activation of Focal Adhesion Kinase

  • Cho, Whajung (Department of Microbiology and Immunology, Kangwon National University School of Medicine) ;
  • Kim, Hyeyoung (Department of Microbiology and Immunology, Kangwon National University School of Medicine) ;
  • Lee, Jeong-Hyung (Department of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Hong, Seung Hee (Department of Food Nutritional Sciences, Hanbuk University) ;
  • Choe, Jongseon (Department of Microbiology and Immunology, Kangwon National University School of Medicine)
  • 투고 : 2013.08.21
  • 심사 : 2013.09.11
  • 발행 : 2013.10.31

초록

Syntenin is an adaptor molecule containing 2 PDZ domains which mediate molecular interactions with diverse integral or cytoplasmic proteins. Most of the results on the biological function of syntenin were obtained from studies with malignant cells, necessitating exploration into the role of syntenin in normal cells. To understand its role in normal cells, we investigated expression and function of syntenin in human lymphoid tissue and cells in situ and in vitro. Syntenin expression was denser in the germinal center than in the extrafollicular area. Inside the germinal center, syntenin expression was obvious in follicular dendritic cells (FDCs). Flow cytometric analysis with isolated cells confirmed a weak expression of syntenin in T and B cells and a strong expression in FDCs. In FDC-like cells, HK cells, most syntenin proteins were found in the cytoplasm compared to weak expression in the nucleus. To study the function of syntenin in FDC, we examined its role in the focal adhesion of HK cells by depleting syntenin by siRNA technology. Knockdown of syntenin markedly impaired focal adhesion kinase phosphorylation in HK cells. These results suggest that syntenin may play an important role in normal physiology as well as in cancer pathology.

키워드

참고문헌

  1. Grootjans, J. J., P. Zimmermann, G. Reekmans, A. Smets, G. Degeest, J. Dürr, and G. David. 1997. Syntenin, a PDZ protein that binds syndecan cytoplasmic domains. Proc. Natl. Acad. Sci. USA. 94: 13683-13688. https://doi.org/10.1073/pnas.94.25.13683
  2. Beekman, J. M. and P. J. Coffer. 2008. The ins and outs of syntenin, a multifunctional intracellular adaptor protein. J. Cell Sci. 121: 1349-1355. https://doi.org/10.1242/jcs.026401
  3. Gibferrer, I., A. Ibanez, M. Farnos, M.-R. Sarrias, R. Funutria, S. Rosello, P. Zimmermann, G. David, J. Vives, C. Serra-Pages, and F. Lozano. 2005. The lymphocyte receptor CD6 interacts with syntenin-1, a scaffolding protein containing PDZ domains. J. Immunol. 175: 1406-1414. https://doi.org/10.4049/jimmunol.175.3.1406
  4. Latysheva, N., G. Muratov, S. Rajesh, M. Padgett, N. A. Hotchin, M. Overduin, and F. Berditchevski. 2006. Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin- 1 with CD63. Mol. Cell. Biol. 26: 7707-7718. https://doi.org/10.1128/MCB.00849-06
  5. Chen, F., Y. Du, Z. Zhang, G. Chen, M. Zhang, H.-B. Shu, Z. Zhai, and D. Chen. 2008. Syntenin negatively regulates TRAF6-mediated IL-1R/TLR4 signaling. Cell Signal. 20: 666-674. https://doi.org/10.1016/j.cellsig.2007.12.002
  6. Koo, T. H., J.-J. Lee, E.-M. Kim, K.-W. Kim, H. D. Kim, and J.-H. Lee. 2002. Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines. Oncogene 21: 4080-4088. https://doi.org/10.1038/sj.onc.1205514
  7. Gangemi, R., V. Mirisola, G. Barisione, M. Fabbi, A. Brizzolara, F. Lanza, C. Mosci, S. Salvi, M. Gualco, M. Truini, G. Angelini, S. Boccardo, M. Cilli, I. Airoldi, P. Queirolo, M. J. Jager, A. Daga, U. Pfeffer, and S. Ferrini. 2012. Mda-9/ Syntenin Is expressed in uveal melanoma and correlates with metastatic progression. PLoS One 7: e29989. https://doi.org/10.1371/journal.pone.0029989
  8. Boukerche, H., Z.-z. Su, C. Prevot, D. Sarkar, and P. B. Fisher. 2008. mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src. Proc. Natl. Acad. Sci. USA. 105: 15914-15919. https://doi.org/10.1073/pnas.0808171105
  9. Choe, J., H.-S. Kim, R. J. Armitage, and Y. S. Choi. 1997. The functional role of BCR stimulation and IL-4 in the generation of human memory B cells from germinal center B cells. J. Immunol. 159: 3757-3766.
  10. Kim, H.-S., X. Zhang, and Y. S. Choi. 1994. Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes. J. Immunol. 153: 2951-2961.
  11. Kim, J., S. Lee, Y.-M. Kim, D.-I. Jeoung, and J. Choe. 2013. Human follicular dendritic cells promote germinal center B cell survival by providing prostaglandins. Mol. Immunol. 55: 418-423. https://doi.org/10.1016/j.molimm.2013.03.019
  12. Cho, W., S. H. Hong, and J. Choe. 2013. IL-4 and HDAC inhibitors suppress cyclooxygenase-2 expression in human follicular dendritic cells. Immune Netw. 13: 75-79. https://doi.org/10.4110/in.2013.13.2.75
  13. Clark, E. A., K. H. Grabstein, and G. L. Shu. 1992. Cultured human follicular dendritic cells: Growth characteristics and interactions with B lymphocytes. J. Immunol. 148: 3327-3335.
  14. Hwangbo, C., J. Kim, J. J. Lee, and J.-H. Lee. 2010. Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase C and the PDZ adapter protein mda-9/syntenin. Cancer Res. 70: 1645-1655. https://doi.org/10.1158/0008-5472.CAN-09-2447
  15. Munoz-Fernandez, R., F. J. Blanco, C. Frecha, F. Martin, M. Kimatrai, A. C. Abadia-Molina, J. M. Carcia-Pacheco, and E. G. Olivares. 2006. Follicular dendritic cells are related to bone marrow stromal cell progenitors and to myofibroblasts. J. Immunol. 177: 280-289. https://doi.org/10.4049/jimmunol.177.1.280
  16. Lindhout, E. and C. de Groot. 1995. Follicular dendritic cells and apoptosis: life and death in the germinal centre. Histochem. J. 27: 167-183. https://doi.org/10.1007/BF02389884
  17. Franchini, K. G. 2012. Focal adhesion kinase - The basis of local hypertrophic signaling domains. J. Mol. Cell. Cardiol. 52: 485-492. https://doi.org/10.1016/j.yjmcc.2011.06.021
  18. Stehbens, S. and T. Wittmann. 2012. Targeting and transport: How microtubules control focal adhesion dynamics. J. Cell Biol. 198: 481-489. https://doi.org/10.1083/jcb.201206050

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