Alteration of the C-terminal amino acid of tubulin specifically inhibits myogenic differentiation

Winston Chang, Daniel R. Webster, Ambar A. Salam, Dorota Gruber, Aparna Prasad, Jason P. Eiserich, J. Chloë Bulinski

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)30690-30698
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number34
DOIs
StatePublished - Aug 23 2002

ASJC Scopus subject areas

  • Biochemistry

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    Chang, W., Webster, D. R., Salam, A. A., Gruber, D., Prasad, A., Eiserich, J. P., & Chloë Bulinski, J. (2002). Alteration of the C-terminal amino acid of tubulin specifically inhibits myogenic differentiation. Journal of Biological Chemistry, 277(34), 30690-30698. https://doi.org/10.1074/jbc.M204930200