Skip to main content
SpringerLink
Log in

Cortactin, an actin binding protein, regulates GLUT4 translocation via actin filament remodeling

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Insulin regulates glucose uptake into fat and skeletal muscle cells by modulating the translocation of GLUT4 between the cell surface and interior. We investigated a role for cortactin, a cortical actin binding protein, in the actin filament organization and translocation of GLUT4 in Chinese hamster ovary (CHO-GLUT4myc) and L6-GLUT4myc myotube cells. Overexpression of wild-type cortactin enhanced insulin-stimulated GLUT4myc translocation but did not alter actin fiber formation. Conversely, cortactin mutants lacking the Src homology 3 (SH3) domain inhibited insulin-stimulated formation of actin stress fibers and GLUT4 translocation similar to the actin depolymerizing agent cytochalasin D. Wortmannin, genistein, and a PP1 analog completely blocked insulin-induced Akt phosphorylation, formation of actin stress fibers, and GLUT4 translocation indicating the involvement of both PI3-K/Akt and the Src family of kinases. The effect of these inhibitors was even more pronounced in the presence of overexpressed cortactin suggesting that the same pathways are involved. Knockdown of cortactin by siRNA did not inhibit insulin-induced Akt phosphorylation but completely inhibited actin stress fiber formation and glucose uptake. These results suggest that the actin binding protein cortactin is required for actin stress fiber formation in muscle cells and that this process is absolutely required for translocation of GLUT4-containing vesicles to the plasma membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zeigerer, A., Lampson, M. A., Karylowski, O., David, D., Adesnik, M., Ren, M., and McGraw, T. E. (2002) Mol. Biol. Cell, 13, 2421–2435.

    Article  PubMed  CAS  Google Scholar 

  2. Furtado, L. M., Somwar, R., Sweeney, G., Niu, W., and Klip, A. (2002) Biochem. Cell. Biol., 80, 569–578.

    Article  PubMed  CAS  Google Scholar 

  3. Wang, Q., Khayat, Z., Kishi, K., Ebina, Y., and Klip, A. (1998) FEBS Lett., 427, 193–197.

    Article  PubMed  CAS  Google Scholar 

  4. Lampson, M. A., Schmoranzer, J., Zeigerer, A., Simon, S., and Mc Graw, T. E. (2001) Mol. Biol. Cell, 12, 3489–3501.

    PubMed  CAS  Google Scholar 

  5. Garza, L., and Birnbaum, M. (2000) J. Biol. Chem., 275, 2560–2567.

    Article  PubMed  CAS  Google Scholar 

  6. Lampson, M. A., Racz, A., Cushman, S. W., and Mc Graw, T. E. (2000) J. Cell Sci., 113, 4065–4076.

    PubMed  CAS  Google Scholar 

  7. Wang, Q., Bilan, P. J., Tsakiridis, T., Hinek, A., and Klip, A. (1998) Biochem. J., 331, 917–928.

    PubMed  CAS  Google Scholar 

  8. Khayat, Z. A., Tong, P., Yaworsky, K., Bloch, R. J., and Klip, A. (2000) J. Cell Sci., 113, 279–290.

    PubMed  CAS  Google Scholar 

  9. Kanai, F., Ito, K., Todaka, M., Hayashi, H., Kamohara, S., Ishii, K., Okada, T., Hazaki, O., Ui, M., and Ebina, Y. (1993) Biochem. Biophys. Res. Commun., 195, 762–768.

    Article  PubMed  CAS  Google Scholar 

  10. Subtil, A., Lampson, M. A., Keller, S. R., and Mc Graw, T. E. (2000) J. Biol. Chem., 275, 4787–4795.

    Article  PubMed  CAS  Google Scholar 

  11. Kanzaki, M., and Pessin, J. E. (2001) J. Biol. Chem., 276, 42436–42444.

    Article  PubMed  CAS  Google Scholar 

  12. Brozinick, J. T., Jr., Hawkins, E. D., Strawbridge, A. B., and Elmendorf, J. S. (2004) J. Biol. Chem., 279, 40699–40706.

    Article  PubMed  CAS  Google Scholar 

  13. Emoto, M., Langille, S. E., and Czech, M. P. (2001) J. Biol. Chem., 276, 10677–10682.

    Article  PubMed  CAS  Google Scholar 

  14. Imamura, T., Huang, J., Usui, I., Satoh, H., Bever, J., and Olefsky, J. M. (2003) Mol. Cell. Biol., 14, 4892–4900.

    Article  Google Scholar 

  15. Semiz, S., Park, J. G., Nicoloro, S. M., Furcinitti, P., Zhang, C., Chawla, A., Leszyk, J., and Czech, M. P. (2003) EMBO J., 22, 2387–2399.

    Article  PubMed  CAS  Google Scholar 

  16. Bose, A., Guilherme, A., Robida, S. I., Nicoloro, S. M., Zhou, Q. L., Jiang, Z. Y., Pomerleau, D. P., and Czech, M. P. (2002) Nature, 420, 821–824.

    Article  PubMed  CAS  Google Scholar 

  17. Huang, J., Imamura, T., Babendure, J. L., Lu, J. C., and Olefsky, J. M. (2005) J. Biol. Chem., 280, 42300–42306.

    Article  PubMed  CAS  Google Scholar 

  18. Ai, H., Ralston, E., Lauritzen, H. P., Galbo, H., and Ploug, T. (2003) Am. J. Physiol. Endocrinol. Metab., 285, E836–844.

    PubMed  CAS  Google Scholar 

  19. Tong, P., Khayat, Z. A., Huang, C., Patel, N., Ueyama, A., and Klip, A. (2001) J. Clin. Invest., 108, 371–381.

    PubMed  CAS  Google Scholar 

  20. Kanzaki, M., Watson, R. T., Khan, A. H., and Pessin, J. E. (2001) J. Biol. Chem., 276, 49331–49336.

    Article  PubMed  CAS  Google Scholar 

  21. Crostella, L., Lidder, S., Williams, R., and Skouteris, G. G. (2001) Oncogene, 20, 3735–3745.

    Article  PubMed  CAS  Google Scholar 

  22. Bourguignon, L. Y., Zhu, H., Shao, L., and Chen, Y. W. (2001) J. Biol. Chem., 276, 7327–7336.

    Article  PubMed  CAS  Google Scholar 

  23. McNiven, M. A., Kim, L., Krueger, E. W., Orth, J. D., Cao, H., and Wong, T. W. (2000) J. Cell. Biol., 151, 187–198.

    Article  PubMed  CAS  Google Scholar 

  24. Uruno, T., Liu, J., Li, Y., Smith, N., and Zhan, X. (2003) J. Biol. Chem., 278, 26086–26093.

    Article  PubMed  CAS  Google Scholar 

  25. Webb, B. A., Eves, R., and Mak, A. S. (2006) Exp. Cell. Res., 312, 760–769.

    Article  PubMed  CAS  Google Scholar 

  26. Torres, E., and Rosen, M. K. (2006) J. Biol. Chem., 281, 3513–3520.

    Article  PubMed  CAS  Google Scholar 

  27. Jiang, Z. Y., Chawla, A., Bose, A., Way, M., and Czech, M. P. (2002) J. Biol. Chem., 277, 509–515.

    Article  PubMed  CAS  Google Scholar 

  28. Schuuring, E., van Damme, H., Schuuring-Scholtes, E., Verhoeven, E., Michalides, R., Geelen, E., de Boer, C., Brok, H., van Buuren, V., and Kluin, P. (1998) Cell. Adhes. Commun., 6, 185–209.

    Article  PubMed  CAS  Google Scholar 

  29. Du, Y., Weed, S. A., Xiong Wen, C., Marshall, T. D., and Parsons, J. T. (1998) Mol. Cell. Biol., 10, 5838–5851.

    Google Scholar 

  30. Wu, H., and Parsons, J. T. (1993) J. Cell Biol., 120, 1417–1426.

    Article  PubMed  CAS  Google Scholar 

  31. Kanai, F., Nishioka, Y., Hayashi, H., Kamohara, S., Todaka, M., and Ebina, Y. (1993) J. Biol. Chem., 268, 14523–14526.

    PubMed  CAS  Google Scholar 

  32. Klip, A., Li, G., and Logan, W. J. (1984) Am. J. Physiol., 247, E291–E296.

    PubMed  CAS  Google Scholar 

  33. Klip, A., Li, G., and Walker, D. (1983) Can. J. Biochem. Cell Biol., 61, 644–649.

    Article  PubMed  CAS  Google Scholar 

  34. Ohoka, Y., and Takai, Y. (1998) Genes Cells, 9, 603–612.

    Article  Google Scholar 

  35. Campbell, D. H., Sutherland, R. L., and Daly, R. J. (1999) Cancer Res., 59, 5376–5385.

    PubMed  CAS  Google Scholar 

  36. Olazabel, I. M., and Machesky, L. M. (2001) J. Cell. Biol., 154, 679–682.

    Article  Google Scholar 

  37. Lopez, I., Duprez, V., Melle, J., Dreyfus, F., Levy-Toledano, S., and Fontenary-Roupie, M. (2001) Biochem. J., 356, 875–881.

    Article  PubMed  CAS  Google Scholar 

  38. Craig, A. W. B., Zirngibl, R., Williams, K., Cole, L., and Greer, P. A. (2001) Mol. Cell. Biol., 21, 603–613.

    Article  PubMed  CAS  Google Scholar 

  39. Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B., and Prossnitz, E. R. (2005) Science, 307, 1625–1630.

    Article  PubMed  CAS  Google Scholar 

  40. Kam, Y., and Exton, J. H. (2001) Mol. Cell. Biol., 21, 4055–4066.

    Article  PubMed  CAS  Google Scholar 

  41. Komati, H., Naro, F., Mebarek, S., de Arcangelis, V., Adamo, S., Lagarde, M., Prigent, A. F., and Nemoz, G. (2005) Mol. Biol. Cell, 16, 1232–1244.

    Article  PubMed  CAS  Google Scholar 

  42. Dawson, C. W., Tramountanis, G., Eliopoulos, A. G., and Young, L. S. (2003) J. Biol. Chem., 278, 3694–3704.

    Article  PubMed  CAS  Google Scholar 

  43. Qian, Y., Corum, L., Meng, Q., Blenis, J., Zheng, J. Z., Shi, X., Flynn, D. C., and Jiang, B. H. (2004) Am. J. Physiol. Cell Physiol., 286, C153–C163.

    Article  PubMed  CAS  Google Scholar 

  44. Torok, D., Patel, N., JeBailey, L., Thong, F. S. L., Randhawa, V. K., Klip, A., and Rudich, A. (2004) J. Cell. Sci., 117, 5447–5455.

    Article  PubMed  Google Scholar 

  45. Omata, W., Shibata, H., Li, L., Takata, K., and Kojima, I. (2000) Biochem. J., 346, 321–328.

    Article  PubMed  CAS  Google Scholar 

  46. Patki, V., Buxton, J., Chawla, A., Lifshitz, L., Fogarty, K., Carrington, W., Tuft, R., and Corvera, S. (2001) Mol. Biol. Cell, 12, 129–141.

    PubMed  CAS  Google Scholar 

  47. Bose, A., Cherniack, A. D., Langille, S. E., Nicoloro, S. M., Buxton, J. M., Park, J. G., Chawla, A., and Czech, M. P. (2001) Mol. Cell. Biol., 15, 5262–5275.

    Article  Google Scholar 

  48. Weaver, A. M., Young, M. E., Lee, W. L., and Cooper, J. A. (2002) Curr. Opin. Cell Biol., 1, 23–30.

    Google Scholar 

  49. Weaver, A. M., Karginov, A. V., Kinley, A. W., Weed, S. A., Yan Li, Parsons, J. T., and Cooper, J. A. (2001) Curr. Biol., 11, 370–374.

    Article  PubMed  CAS  Google Scholar 

  50. May, R. C. (2001) Cell. Mol. Life Sci., 58, 1607–1626.

    Article  PubMed  CAS  Google Scholar 

  51. Higgs, H. N., and Pollard, T. D. (2001) Annu. Rev. Biochem., 70, 649–676.

    Article  PubMed  CAS  Google Scholar 

  52. Usui, I., Imamura, T., Huang, J., Satoh, H., and Olefsky, J. M. (2003) J. Biol. Chem., 278, 13765–13774.

    Article  PubMed  CAS  Google Scholar 

  53. Kanzaki, M., Watson, R. T., Hou, J. C., Stamnes, M., Saltiel, A. R., and Pessin, J. E. (2002) Mol. Biol. Cell, 13, 2334–2346.

    Article  PubMed  CAS  Google Scholar 

  54. Martin, S. S., Haruta, T., Morris, A. J., Klippel, A., Williams, L. T., and Olefsky, J. M. (1996) J. Biol. Chem., 271, 17605–17608.

    Article  PubMed  CAS  Google Scholar 

  55. Unsworth, K. E., Way, M., McNiven, M., Machesky, L., and Holden, D. W. (2004) Cell Microbiol., 11, 1041–1055.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18 Kuramoto-cho, Tokushima, 770-8503, Japan

    H. Nazari, A. Takahashi, N. Harada, M. Nakano & Y. Nakaya

  2. Division of Molecular Genetics, Institute for Enzyme Research, University of Tokushima, Tokushima, 770-8503, Japan

    H. Nazari, K. Kishi & Y. Ebina

  3. Department of Biochemistry and Hematology, Semnan University of Medical Science, Semnan, Iran

    H. Nazari & A. Khaleghian

  4. Department of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA

    N. J. G. Webster

Authors
  1. H. Nazari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Khaleghian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. J. G. Webster
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Kishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y. Ebina
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y. Nakaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Nakaya.

Additional information

Published in Russian in Biokhimiya, 2011, Vol. 76, No. 11, pp. 1566–1575.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nazari, H., Khaleghian, A., Takahashi, A. et al. Cortactin, an actin binding protein, regulates GLUT4 translocation via actin filament remodeling. Biochemistry Moscow 76, 1262–1269 (2011). https://doi.org/10.1134/S0006297911110083

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297911110083

Key words

Search

Navigation