O-GlcNAcylation of tubulin inhibits its polymerization

Suena Ji1, Jeong Gu Kang, Sang Yoon Park

  • 1Department of Biology, Yonsei University, Seoul, Korea.

Amino Acids
|July 29, 2010
PubMed

Insights

O-linked β-N-acetylglucosamine (O-GlcNAc) modification of tubulin inhibits microtubule formation and neurite outgrowth. This protein glycosylation process, O-GlcNAcylation, negatively regulates tubulin polymerization, impacting neuronal development.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification regulating numerous cellular processes.
  • Neurite outgrowth, crucial for neuronal development, is influenced by various signaling pathways and protein modifications.

Purpose of the Study:

  • To investigate the role of O-GlcNAc modification in all-trans retinoic acid (tRA)-induced neurite outgrowth.
  • To identify proteins undergoing O-GlcNAc modification during neuronal differentiation.

Main Methods:

  • Mass spectrometric analysis to identify O-GlcNAcylated proteins.
  • Western blotting and peptide mapping to confirm tubulin O-GlcNAcylation.
  • In vitro polymerization assays and cell culture experiments.

Main Results:

  • O-GlcNAc modification patterns changed during tRA-induced neurite outgrowth in MN9D cells.
  • α- and β-tubulin were identified as O-GlcNAcylated proteins.
  • Increased O-GlcNAcylation of tubulin reduced heterodimerization and polymerization, inhibiting microtubule formation and decreasing neurite outgrowth by 20% when O-GlcNAcase inhibitors were used.

Conclusions:

  • Tubulin O-GlcNAcylation negatively regulates microtubule formation.
  • O-GlcNAc modification plays a critical role in controlling neurite outgrowth during neuronal differentiation.

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