TY - JOUR
T1 - Alteration of the C-terminal amino acid of tubulin specifically inhibits myogenic differentiation
AU - Chang, Winston
AU - Webster, Daniel R.
AU - Salam, Ambar A.
AU - Gruber, Dorota
AU - Prasad, Aparna
AU - Eiserich, Jason P.
AU - Chloë Bulinski, J.
PY - 2002/8/23
Y1 - 2002/8/23
N2 - Detyrosination is an evolutionarily conserved post-translational modification of microtubule polymers that is known to be enhanced during early morphological differentiation of cultured myogenic cells (Gundersen, G. G., Khawaja, S., and Bulinski, J. C. (1989) J. Cell Biol. 109, 2275-2288). We proposed that altering the C terminus of α-tubulin by detyrosination plays a role in morphological differentiation. To test our hypothesis, we treated L6 myoblasts with 3-nitrotyrosine (Eiserich, J. P., Estevez, A. G., Bamberg, T. V., Ye, Y. Z., Chumley, P. H., Beckman, J. S., and Freeman, B. A. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 6365-6375), a nontoxic inhibitor that resulted in high level inhibition of microtubule detyrosination and low level incorporation of nitrotyrosine into microtubules. Even though microtubule stabilization or modification by acetylation still occurred normally, morphological differentiation was blocked; myoblasts neither elongated significantly nor fused. Nitrotyrosine treatment prevented synthesis or activation of markers of myogenic differentiation, including muscle-specific myosin, α-actin, integrin α7, and myogenin. Consistent with this, myoblast integrin β1A remained highly expressed. In contrast, the increase in β-catenin level characteristic of early myogenesis was unaffected by treatment. These results show that the identity of the C-terminal residue of a-tubulin modulates microtubule activity, possibly because binding to or signaling from modified microtubules is required for the myogenic program.
AB - Detyrosination is an evolutionarily conserved post-translational modification of microtubule polymers that is known to be enhanced during early morphological differentiation of cultured myogenic cells (Gundersen, G. G., Khawaja, S., and Bulinski, J. C. (1989) J. Cell Biol. 109, 2275-2288). We proposed that altering the C terminus of α-tubulin by detyrosination plays a role in morphological differentiation. To test our hypothesis, we treated L6 myoblasts with 3-nitrotyrosine (Eiserich, J. P., Estevez, A. G., Bamberg, T. V., Ye, Y. Z., Chumley, P. H., Beckman, J. S., and Freeman, B. A. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 6365-6375), a nontoxic inhibitor that resulted in high level inhibition of microtubule detyrosination and low level incorporation of nitrotyrosine into microtubules. Even though microtubule stabilization or modification by acetylation still occurred normally, morphological differentiation was blocked; myoblasts neither elongated significantly nor fused. Nitrotyrosine treatment prevented synthesis or activation of markers of myogenic differentiation, including muscle-specific myosin, α-actin, integrin α7, and myogenin. Consistent with this, myoblast integrin β1A remained highly expressed. In contrast, the increase in β-catenin level characteristic of early myogenesis was unaffected by treatment. These results show that the identity of the C-terminal residue of a-tubulin modulates microtubule activity, possibly because binding to or signaling from modified microtubules is required for the myogenic program.
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U2 - 10.1074/jbc.M204930200
DO - 10.1074/jbc.M204930200
M3 - Article
C2 - 12070174
AN - SCOPUS:0037163058
VL - 277
SP - 30690
EP - 30698
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 34
ER -