Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Regulation of m-Calpain Activity by α-Synuclein and Its C-terminal Fragment (α-syn61-140)

  • Lee, In-Hwan (School of Chemical and Biological Engineering, College of Engineering, Seoul National University) ;
  • Kim, Hyun-Jin (School of Chemical and Biological Engineering, College of Engineering, Seoul National University) ;
  • Lee, Choong-Hwan (School of Chemical and Biological Engineering, College of Engineering, Seoul National University) ;
  • Paik, Seung R. (School of Chemical and Biological Engineering, College of Engineering, Seoul National University)
  • Published : 2006.01.20
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Abstract

The m-calpain activity hydrolyzing a fluorogenic substrate of N-Succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcourmarin (LLVY-AMC) was significantly stimulated by more than two-fold in the presence of 5$\mu$M $\alpha$synuclein at $15{^{\circ}C}$. The stimulation was also confirmed with azocasein. The stimulation of the peptide hydrolyzing activity required structural intactness of $\alpha$-synuclein since the C-terminally or N-terminally modified proteins such as $\beta$-synuclein, $\alpha$-syn1-97, and $\alpha$-syn61-140 did not increase the proteolytic activity. Instead, however, the N-terminally truncated $\alpha$-syn61-140 was shown to drastically suppress the calpain activity. Since the N-terminal truncation was known to be the primary cleaving event of calpain-mediated proteolysis of $\alpha$-synuclein and the $\alpha$-syn61-140 has been demonstrated to be resistant against the calpain digestion, it has been proposed that the intracellular calpain activity could be regulated in a reciprocal manner by $\alpha$-synuclein and its proteolyzed C-terminal fragment. Based on the results, a possible physiological function of $\alpha$-synuclein has been suggested as a calpain regulator which contains both stimulatory and inhibitory activities.

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References

  1. Abeliovich, A.; Schmitz, Y.; Farinas, I.; Choi-Lundberg, D.; Ho, W. H.; Castillo, P. E.; Shinsky, N.; Verdugo, J. M.; Armanini, M.; Ryan, A.; Hynes, M.; Phillips, H. K.; Sulzer, D.; Rosenthal, A. Neuron 2000, 25, 239 https://doi.org/10.1016/S0896-6273(00)80886-7
  2. Polymeropoulos, M. H.; Lavedan, C.; Leroy, E.; Ide, S. E.; Dehejia, A.; Dutra, A.; Pike, B.; Root, H.; Rubenstein, J.; Boyer, R.; Stenroos, E. S.; Chandrasekharappa, S.; Athanassiadou, A.; Papapetropoulos, T.; Johnson, W. G.; Lazzarini, A. M.; Duvoisin, R. C.; Iorio, G. D.; Golbe, L. I.; Nussbaum, R. L. Science 1997, 276, 2045 https://doi.org/10.1126/science.276.5321.2045
  3. Dickson, D. W. Curr. Opin. Neurol. 2001, 14, 423 https://doi.org/10.1097/00019052-200108000-00001
  4. Goedert, M. Nature 1997, 388, 232
  5. Clayton, D. F.; George, J. M. Trends Neurosci. 1998, 21, 249 https://doi.org/10.1016/S0166-2236(97)01213-7
  6. Clayton, D. F.; George, J. M. J. Neurosci. Res. 1999, 58, 120 https://doi.org/10.1002/(SICI)1097-4547(19991001)58:1<120::AID-JNR12>3.0.CO;2-E
  7. Lee, F. J. S.; Liu, F.; Pristupa, Z. B.; Niznik, H. B. FASEB J. 2001, 15, 916 https://doi.org/10.1096/fj.00-0334com
  8. Perez, R. G.; Waymire, J. C.; Lin, E.; Liu, J. J.; Guo, F.; Zigmond, M. J. J. Neurosci. 2002, 22, 3090
  9. Sung, J. Y.; Kim, J.; Paik, S. R.; Park, J. H.; Ahn, Y. S.; Chung, K. C. J. Biol. Chem. 2001, 276, 27441 https://doi.org/10.1074/jbc.M101318200
  10. Iwata, A.; Maruyama, M.; Kanazawa, I.; Nukina, N. J. Biol. Chem. 2001, 276, 45320 https://doi.org/10.1074/jbc.M103736200
  11. Weinreb, P. H.; Zhen, W.; Poon, A. W.; Conway, K. A.; Lansbury, P. T. Biochemistry 1996, 35, 13709 https://doi.org/10.1021/bi961799n
  12. Kim, J. Mol. Cells 1997, 7, 78
  13. Lee, D.; Lee, S.-Y.; Lee, E.-N.; Chang, C.-S.; Paik, S. R. J. Neurochem. 2002, 82, 1007 https://doi.org/10.1046/j.1471-4159.2002.01024.x
  14. Wang, K. K.; Villalobo, A.; Roufogalis, B. D. Biochem. J. 1989, 262, 693 https://doi.org/10.1042/bj2620693
  15. Demartino, G. N.; Blumenthal, D. K. Biochemistry 1982, 21, 4297 https://doi.org/10.1021/bi00261a019
  16. Takeyama, Y.; Nakanishi, H.; Uratsuji, Y.; Kishimoto, A.; Nishizuka, Y. FEBS Lett. 1986, 194, 110 https://doi.org/10.1016/0014-5793(86)80060-6
  17. Paik, S. R.; Lee, J. H.; Kim, D. H.; Chang, C. S.; Kim, J. Arch. Biochem. Biophys. 1997, 344, 325 https://doi.org/10.1006/abbi.1997.0207
  18. Davidson, W. S.; Jonas, A.; Clayton, D. F.; George, J. M. J. Biol. Chem. 1998, 273, 9443 https://doi.org/10.1074/jbc.273.16.9443
  19. Jo, E.; McLaurin, J.; Yip, C. M.; George-Hyslop, P.; St. Fraser, P. E. J. Biol. Chem. 2000, 275, 34328 https://doi.org/10.1074/jbc.M004345200
  20. Leng, Y.; Chase, T. N.; Bennett, M. C. J. Biol. Chem. 2001, 276, 28212 https://doi.org/10.1074/jbc.M011121200
  21. Perrin, R. J.; Woods, W. S.; Clayton, D. F.; George, J. M. J. Biol. Chem. 2001, 276, 41958 https://doi.org/10.1074/jbc.M105022200
  22. Sharon, R.; Goldberg, M. S.; Bar-Josef, I.; Betensky, R. A.; Shen, J.; Selkoe, D. J. Proc. Natl. Acad. Sci. USA 2001, 98, 9110 https://doi.org/10.1073/pnas.171300598
  23. Croall, D. E.; DeMartino, G. N. Physiol. Rev. 1991, 71, 813 https://doi.org/10.1152/physrev.1991.71.3.813
  24. Hosfield, C. M.; Moldoveanu, T.; Davies, P. L.; Elce, J. S.; Jia, Z. J. Biol. Chem. 2001, 276, 7404 https://doi.org/10.1074/jbc.M007352200
  25. Cong, J. Y.; Goll, D. E.; Peterson, A. M.; Kapprell, H. P. J. Biol. Chem. 1989, 264, 10096
  26. Inomata, M.; Hayashi, M.; Nakamura, M.; Saito, Y.; Kawashima, S. J. Biol. Chem. 1989, 264, 18838
  27. Inomata, M.; Saito, Y.; Kon, K.; Kawashima, S. Biochem. Biophys. Res. Commun. 1990, 171, 625 https://doi.org/10.1016/0006-291X(90)91192-U
  28. Paik, S. R.; Shin, H.-J.; Lee, J.-H.; Chang, C.-S.; Kim, J. Biochem. J. 1999, 340, 821 https://doi.org/10.1042/0264-6021:3400821
  29. Paik, S. R.; Lee, D.; Cho, H.-J.; Lee, E.-N.; Chang, C.-S. FEBS Lett. 2003, 537, 63 https://doi.org/10.1016/S0014-5793(03)00081-4
  30. Dayton, W. R.; Reville, W. J.; Goll, D. E.; Stromer, M. H. Biochemistry 1976, 15, 2159 https://doi.org/10.1021/bi00655a020
  31. Mishizen-Eberz, A. J.; Guttmann, R. P.; Giasson, B. I.; Day, G. A. 3rd; Hodara, R.; Ischiropoulos, H.; Lee, V. M.; Trojanowski, J. Q.; Lynch, D. R. J. Neurochem. 2003, 86, 836 https://doi.org/10.1046/j.1471-4159.2003.01878.x

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