The N-terminal domain of the myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase: Direct molecular interaction with the calcium sensor calmodulin

Matti Myllykoski, Kouichi Itoh, Salla M. Kangas, Anthony M. Heape, Sung Ung Kang, Gert Lubec, Inari Kursula, Petri Kursula

Research output: Contribution to journalArticle

Abstract

2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is a quantitatively major enzyme in myelin, where it localizes to the non-compact regions and is bound to the membrane surface. Although its catalytic activity in vitro has been characterized, the physiological function and in vivo substrate of CNPase remain unknown. Especially the N-terminal domain has been poorly characterized; previously, we have shown it is involved in CNPase dimerization and RNA binding. Here, we show that purified CNPase binds to the calcium sensor protein calmodulin (CaM) in a calcium-dependent manner; the binding site is in the N-terminal domain of CNPase. CaM does not affect the phosphodiesterase activity of CNPase in vitro, nor does it influence polyadenylic acid binding. The colocalization of CNPase and CaM during Schwann cell myelination in culture was observed, and CaM antagonists induced the colocalization of CNPase with microtubules in differentiated CG-4 oligodendrocytes. An analysis of post-translational modifications of CNPase from rat brain revealed the presence of two novel phosphorylation sites on Tyr110 and Ser169 within the N-terminal domain. The results indicate a role for the N-terminal domain of CNPase in mediating multiple molecular interactions and provide a starting point for detailed structure-function studies on CNPase and its N-terminal domain.

Original languageEnglish (US)
Pages (from-to)515-524
Number of pages10
JournalJournal of Neurochemistry
Volume123
Issue number4
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • 2',3'-cyclic nucleotide 3'-phosphodiesterase
  • calmodulin
  • interaction
  • myelin
  • protein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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