O-GlcNAcylation of tubulin inhibits its polymerization

Suena Ji, Jeong Gu Kang, Sang Yoon Park, Joohun Lee, Young J. Oh, Jin Won Cho

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins is an abundant and reversible modification that involves many cellular processes including transcription, translation, cell proliferation, apoptosis, and signal transduction. Here, we found that the O-GlcNAc modification pattern was altered during all-trans retinoic acid (tRA)-induced neurite outgrowth in the MN9D neuronal cell line. We identified several O-GlcNAcylated proteins using mass spectrometric analysis, including α- and β-tubulin. Further analysis of α- and β-tubulin revealed that O-GlcNAcylated peptides mapped between residues 173 and 185 of α-tubulin and between residues 216 and 238 of β-tubulin, respectively. We found that an increase in α-tubulin O-GlcNAcylation reduced heterodimerization and that O-GlcNAcylated tubulin did not polymerize into microtubules. Consequently, when O-GlcNAcase inhibitors were co-incubated with tRA, the extent of neurite outgrowth was decreased by 20% compared to control. Thus, our data indicate that the O-GlcNAcylation of tubulin negatively regulates microtubule formation.

Original languageEnglish
Pages (from-to)809-818
Number of pages10
JournalAmino Acids
Volume40
Issue number3
DOIs
Publication statusPublished - 2011 Mar

Bibliographical note

Funding Information:
This work was supported by grants from National Research Foundation funded by the Ministry of Education, Science and Technology Grant (R0A-2007-000-20011-0), and WCU project (R31-2008-000-10086-0). In addition, S.J., S.Y.P. and J.G.K. are fellowship awardees of the Brain Korea 21 program. This work was made possible through the use of research facilities in the Yonsei Center for Biotechnology.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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