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The N‐terminal domain of the myelin enzyme 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase: direct molecular interaction with the calcium sensor calmodulin
Author(s) -
Myllykoski Matti,
Itoh Kouichi,
Kangas Salla M.,
Heape Anthony M.,
Kang SungUng,
Lubec Gert,
Kursula Inari,
Kursula Petri
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12000
Subject(s) - calmodulin , colocalization , phosphodiesterase , biology , microbiology and biotechnology , myelin basic protein , biochemistry , myelin , enzyme , central nervous system , neuroscience
2′,3′‐cyclic nucleotide 3′‐phosphodiesterase ( CNP ase) 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 CNP ase remain unknown. Especially the N‐terminal domain has been poorly characterized; previously, we have shown it is involved in CNP ase dimerization and RNA binding. Here, we show that purified CNP ase binds to the calcium sensor protein calmodulin (CaM) in a calcium‐dependent manner; the binding site is in the N‐terminal domain of CNP ase. CaM does not affect the phosphodiesterase activity of CNP ase in vitro , nor does it influence polyadenylic acid binding. The colocalization of CNP ase and CaM during Schwann cell myelination in culture was observed, and CaM antagonists induced the colocalization of CNP ase with microtubules in differentiated CG ‐4 oligodendrocytes. An analysis of post‐translational modifications of CNP ase 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 CNP ase in mediating multiple molecular interactions and provide a starting point for detailed structure‐function studies on CNP ase and its N‐terminal domain.