Role of Ser50 phosphorylation in SCG10 regulation of microtubule depolymerization

Tetsuya Togano, Masashi Karachi, Michitoshi Watanabe, Gabriele Grenningloh, Michihiro Igarashi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Members of the stathmin-like protein family depolymerize microtubules (MTs), probably due to the ability of each stathmin monomer to bind two tubulin heterodimers in a complex (T2S complex). SCG10, a member of this family, is localized in the growth cone of neurons. It has four identified sites of serine phosphorylation (S50, S63, S73, and S97). Of these, S50 and S97 are phosphorylated by cAMP-dependent protein kinase, an enzyme involved in growth cone guidance. When the equivalent sites in stathmins are phosphorylated, they lose their ability to depolymerize MTs. We investigated the specific role of the two cAMP-dependent protein kinase (PKA) phosphorylation sites in SCG10. A mutant of SCG10 phosphorylated only on S50 retained the ability to depolymerize MTs, but SCG10 phosphorylated on S97 or on both S50 and S97 lost MT-depolymerizing activity. Surface plasmon resonance studies revealed that the phosphorylation of SCG10 at these sites reduced the tubulin heterodimer binding, mainly due to a reduced rate of association. In particular, compared to the two other phosphorylated forms, SCG10 phosphorylated at S50 had a significantly smaller dissociation constant for the binding of the first tubulin heterodimer and larger association and dissociation rate constants for the binding of the second heterodimer. This indicates that the phosphorylation of S50 compensates for the effect of phosphorylation at other sites by modulating T2S complex formation. Furthermore, these results suggest that S50-P maintains MT-depolymerizing activity, which indicates that the biological functions of phosphorylation at S50 and S97 are different.

Original languageEnglish
Pages (from-to)475-480
Number of pages6
JournalJournal of Neuroscience Research
Volume80
Issue number4
DOIs
Publication statusPublished - 2005 May 15

Keywords

  • CAMP-dependent protein kinase
  • Growth cone
  • Microtubules
  • Phosphorylation
  • Surface plasmon resonance

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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